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Sample records for rodent carcinogenic potential

  1. The in vivo rodent test systems for assessment of carcinogenic potential

    DEFF Research Database (Denmark)

    van der Laan, Jan-Willem; Spindler, Per

    2002-01-01

    A Drug Information Association (DIA) workshop was held in May 2001 to discuss the outcome of the International Life Sciences Institute-Health and Environmental Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity assessment such as the P53(+/-) and XPA(+/-) knockout...... mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study...... (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic...

  2. Ranking the potential carcinogenic hazards to workers from exposures to chemicals that are tumorigenic in rodents.

    OpenAIRE

    Gold, L S; Backman, G M; Hooper, N K; Peto, R.

    1987-01-01

    For 41 chemicals there exist both reasonable data on carcinogenic potency in experimental animals and also a defined Permissible Exposure Level (PEL), which is the upper limit of legally permissible chronic occupational exposure for U.S. workers. These 41 agents are ranked by an index that compares the permitted chronic human exposure to the chronic dose rate that induces tumors in 50% of laboratory animals. This index, the Permitted Exposure/Rodent Potency index, or PERP, does not estimate a...

  3. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

    Science.gov (United States)

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-03-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.

  4. International Conference on Harmonisation; proposed change to rodent carcinogenicity testing of pharmaceuticals; request for comments. Notice; request for comments.

    Science.gov (United States)

    2013-03-18

    The Food and Drug Administration (FDA or the Agency) is considering a proposed change to the International Conference on Harmonisation (ICH) Sl guidance on rodent carcinogenicity testing. The goal of this potential change is to introduce a more comprehensive and integrated approach to address the risk of human carcinogenicity of small molecule pharmaceuticals, and to define conditions under which 2-year rodent carcinogenicity studies add value to that assessment. The basis of this proposed change is the retrospective analyses of several datasets that reflect three decades of experience with such studies. The datasets suggest that knowledge of certain pharmacologic and toxicologic data can sometimes provide sufficient information to anticipate the outcome of 2-year rodent studies and their potential value in predicting the risk of human carcinogenicity of a given pharmaceutical. FDA is requesting public comment regarding a proposed change in approach to carcinogenicity assessment, on the prospective evaluation period intended to test this new approach, and on the proposed weight-of-evidence factors for carcinogenicity assessment.

  5. Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents.

    Science.gov (United States)

    van den Brink, Willem; Emerenciana, Annette; Bellanti, Francesco; Della Pasqua, Oscar; van der Laan, Jan Willem

    2017-04-01

    Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes.

  6. Predicting the carcinogenicity of chemicals in humans from rodent bioassay data

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, G. (Harvard Univ., Cambridge, MA (United States) School of Public Health, Boston, MA (United States)); Wilson, R. (Harvard Univ., Cambridge, MA (United States))

    1991-08-01

    Regulatory agencies currently rely on rodent carcinogenicity bioassay data to predict whether or not a given chemical poses a carcinogenic threat to humans. The authors argue that it is always more useful to know a chemical's carcinogenic potency (with confidence limits) than to be able to say only qualitatively that it has been found to be a carcinogen. In a typical bioassay, a chemical is administered to groups of 50 to 100 rodents at the highest feasible level (the maximum tolerated dose) and rarely at less than 1/10 this dose in order to maximize the statistical significance of any increase in tumors that might result. Recently, much experimental work has focused on the mechanisms by which site-specific toxicity arising from chronic administration at the maximum tolerated dose may lead to carcinogenicity. Extrapolation of high-dose results to low dose does not take into consideration the possibility of a threshold dose, below which the carcinogenic potency is much lower or even zero. Threshold dose-response phenomena may be much more relevant to the etiology of cancer in the rodent bioassays than was earlier realized; if so, there is an even greater need for establishing dose-dependent potency estimates. The emphasis of this review is in the interspecies comparison of high-dose potencies. The qualitative and quantitative comparison of carcinogenicities between mice and rats and between rodents and humans is reviewed and discussed. They conclude that there is a good qualitative (yes/no) correlation for both the rat/mouse and the rodent/human comparison.

  7. Improving the power of long term rodent carcinogenicity bioassays by adjusting the experimental design.

    Science.gov (United States)

    Jackson, Matthew T

    2015-07-01

    Since long term rodent carcinogenicity studies are used to test a very large number of potential tumor endpoints, finding a balance between the control of Type 1 and Type 2 error is challenging. As a result, these studies can suffer from very low power to detect effects of regulatory significance. In the present paper, a new design is proposed in order address this problem. This design is a simple modification of the existing standard designs and uses the same number of animals. Where it differs from the currently used designs is that it uses just three treatment groups rather than four, with the animals concentrated in the control and high dose groups, rather than being equally distributed among the groups. This new design is tested, in a pair of simulation studies over a range of scenarios, against two currently used designs, and against a maximally powerful two group design. It consistently performs at levels close to the optimal design, and except in the case of relatively modest effects and very rare tumors, is found to increase power by 10%-20% over the current designs while maintaining or reducing the Type 1 error rate.

  8. Evaluation of the sensitivity and specificity of in vivo erythrocyte micronucleus and transgenic rodent gene mutation tests to detect rodent carcinogens.

    Science.gov (United States)

    Morita, Takeshi; Hamada, Shuichi; Masumura, Kenichi; Wakata, Akihiro; Maniwa, Jiro; Takasawa, Hironao; Yasunaga, Katsuaki; Hashizume, Tsuneo; Honma, Masamitsu

    2016-05-01

    Sensitivity and/or specificity of the in vivo erythrocyte micronucleus (MN) and transgenic rodent mutation (TGR) tests to detect rodent carcinogens and non-carcinogens were investigated. The Carcinogenicity and Genotoxicity eXperience (CGX) dataset created by Kirkland et al. was used for the carcinogenicity and in vitro genotoxicity data, i.e., Ames and chromosome aberration (CA) tests. Broad literature surveys were conducted to gather in vivo MN or TGR test data to add to the CGX dataset. Genotoxicity data in vitro were also updated slightly. Data on 379 chemicals (293 carcinogens and 86 non-carcinogens) were available for the in vivo MN test; sensitivity, specificity or concordances were calculated as 41.0%, 60.5% or 45.4%, respectively. For the TGR test, data on 80 chemicals (76 carcinogens and 4 non-carcinogens) were available; sensitivity was calculated as 72.4%. Based on the recent guidance on genotoxicity testing strategies, performance (sensitivity/specificity) of the following combinations was calculated; Ames+in vivo MN (68.7%/45.3%), Ames+TGR (83.8%/not calculated (nc)), Ames+in vitro CA+in vivo MN (80.8%/21.3%), Ames+in vitro CA+TGR (89.1%/nc), Ames+in vivo MN+TGR (87.5%/nc), Ames+in vitro CA+in vivo MN+TGR (89.3%/nc). Relatively good balance in performance was shown by the Ames+in vivo MN in comparison with Ames+in vitro CA (74.3%/37.5%). Ames+TGR and Ames+in vivo MN+TGR gave even higher sensitivity, but the specificity could not be calculated (too few TGR data on non-carcinogens). This indicates that in vivo MN and TGR tests are both useful as in vivo tests to detect rodent carcinogens.

  9. Evaluation of the carcinogenic potential of pharmaceuticals. Opportunities arising from the International Conference on Harmonisation.

    Science.gov (United States)

    Monro, A M; MacDonald, J S

    1998-05-01

    The evaluation of the carcinogenic potential of pharmaceuticals is currently undergoing dramatic changes. For the past 25 years the regulatory expectation for agents intended for long term use has been that lifespan studies (usually lasting 2 years) in 2 rodent species be conducted. These studies take at least 3 years to plan, execute and interpret, and use over 1200 animals. It is now recognised that the quality of the information obtained from these studies is unreliable for prediction of carcinogenic risk to humans. Over the past 4 years, the International Conference on Harmonisation (ICH) has recommended changes in approaches to assessing the carcinogenic potential of pharmaceuticals. In future, only one long term rodent study will be routinely required (usually in rats), provided this is complemented with a short or medium term test in one of the emerging new models for carcinogenicity, such as transgenic mice or newborn mice. However, the relevance of these new models to human cancer and their use in risk assessment is still largely unknown and this situation must be kept under review as knowledge accumulates. A long term study in a second rodent species is still an option. Dose selection has also been improved inasmuch as there are now several alternatives to the use of the maximum tolerated dose (MTD). In the past, the use of the MTD, when the normal homeostasis of the test animals is disturbed, has been considered one of the major problems with the rodent carcinogenicity bioassay. However, one of the alternative end-points to the use of the MTD, i.e. the comparison of plasma concentrations in rodents and humans, must be viewed with caution. While this may contribute to limiting the high dose level for agents of very low toxicity, the concept should not be interpreted as signifying that plasma concentrations provide a sound basis for comparing the carcinogenic activity of agents in different species. Recognition of the 4 properties (genotoxicity

  10. Evaluation of the potential carcinogenicity of chlorambucil. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1988-06-01

    Chlorambucil is a probable human carcinogen, classified as weight-of-evidence Group B1 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is Limited. Data available are inadequate for calculating a potency factor (F) and no quantitative inferences can be made according to the CAG's methodology for evaluating potential carcinogens. Chlorambucil is, therefore, assigned to the median potency factor range and placed in potency group 2. Combining the weight-of-evidence group and the potency group, chlorambucil is assigned a MEDIUM hazard ranking.

  11. JaCVAM-organized international validation study of the in vivo rodent alkaline comet assay for detection of genotoxic carcinogens: II. Summary of definitive validation study results.

    Science.gov (United States)

    Uno, Yoshifumi; Kojima, Hajime; Omori, Takashi; Corvi, Raffaella; Honma, Masamistu; Schechtman, Leonard M; Tice, Raymond R; Beevers, Carol; De Boeck, Marlies; Burlinson, Brian; Hobbs, Cheryl A; Kitamoto, Sachiko; Kraynak, Andrew R; McNamee, James; Nakagawa, Yuzuki; Pant, Kamala; Plappert-Helbig, Ulla; Priestley, Catherine; Takasawa, Hironao; Wada, Kunio; Wirnitzer, Uta; Asano, Norihide; Escobar, Patricia A; Lovell, David; Morita, Takeshi; Nakajima, Madoka; Ohno, Yasuo; Hayashi, Makoto

    2015-07-01

    The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this exercise was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The study protocol was optimized in the pre-validation studies, and then the definitive (4th phase) validation study was conducted in two steps. In the 1st step, assay reproducibility was confirmed among laboratories using four coded reference chemicals and the positive control ethyl methanesulfonate. In the 2nd step, the predictive capability was investigated using 40 coded chemicals with known genotoxic and carcinogenic activity (i.e., genotoxic carcinogens, genotoxic non-carcinogens, non-genotoxic carcinogens, and non-genotoxic non-carcinogens). Based on the results obtained, the in vivo comet assay is concluded to be highly capable of identifying genotoxic chemicals and therefore can serve as a reliable predictor of rodent carcinogenicity.

  12. Rodents as potential couriers for bioterrorism agents.

    Science.gov (United States)

    Lõhmus, Mare; Janse, Ingmar; van de Goot, Frank; van Rotterdam, Bart J

    2013-09-01

    Many pathogens that can cause major public health, economic, and social damage are relatively easily accessible and could be used as biological weapons. Wildlife is a natural reservoir for many potential bioterrorism agents, and, as history has shown, eliminating a pathogen that has dispersed among wild fauna can be extremely challenging. Since a number of wild rodent species live close to humans, rodents constitute a vector for pathogens to circulate among wildlife, domestic animals, and humans. This article reviews the possible consequences of a deliberate spread of rodentborne pathogens. It is relatively easy to infect wild rodents with certain pathogens or to release infected rodents, and the action would be difficult to trace. Rodents can also function as reservoirs for diseases that have been spread during a bioterrorism attack and cause recurring disease outbreaks. As rats and mice are common in both urban and rural settlements, deliberately released rodentborne infections have the capacity to spread very rapidly. The majority of pathogens that are listed as potential agents of bioterrorism by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases exploit rodents as vectors or reservoirs. In addition to zoonotic diseases, deliberately released rodentborne epizootics can have serious economic consequences for society, for example, in the area of international trade restrictions. The ability to rapidly detect introduced diseases and effectively communicate with the public in crisis situations enables a quick response and is essential for successful and cost-effective disease control.

  13. Expression of p27Kip1, a cell cycle repressor protein, is inversely associated with potential carcinogenic risk in the genetic rodent models of obesity and long-lived Ames dwarf mice.

    Science.gov (United States)

    Eto, Isao

    2013-06-01

    The association of genetic rodent models of obesity and cancer still remains a controversial issue. Although this controversy has largely been resolved in recent years for homozygous leptin receptor-deficient obese Zucker rats and homozygous long-lived Ames dwarf mice, it is still unresolved for homozygous leptin-deficient obese ob/ob mice. The objective of the present study described below was to investigate whether the expression of the cell cycle repressor protein p27(Kip1) is (a) down-regulated in the tumor-free homozygous leptin receptor-deficient obese Zucker rats as well as tumor-free homozygous leptin-deficient obese ob/ob mice and (b) up-regulated in the tumor-free homozygous long-lived Ames dwarf mice. To achieve this objective, we first performed western immunoblot analysis of the hepatic expression of p27. We then performed western immunoblot analysis and proteomic analysis of the hepatic expression of the proteins involved in the upstream molecular signaling pathways for the expression of p27. Lastly, we analyzed the serum levels of glucose, insulin, and branched-chain amino acids, all of which have been shown to regulate, causally and inversely, the expression of p27. The results indicated that the hepatic expression of p27 was down-regulated in the homozygous leptin receptor-deficient obese Zucker rats and up-regulated in the homozygous long-lived Ames dwarf mice as expected. We also found that the hepatic expression of p27 was down-regulated in the homozygous leptin-deficient obese ob/ob mice. This last observation was not completely consistent with all of the results of the published studies where homozygous leptin-deficient obese ob/ob mice were used. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. The dermal carcinogenic potential of unrefined and hydrotreated lubricating oils.

    Science.gov (United States)

    McKee, R H; Daughtrey, W C; Freeman, J J; Federici, T M; Phillips, R D; Plutnick, R T

    1989-08-01

    Unrefined lubricating oils contain relatively high levels of polycyclic aromatic hydrocarbons (PAH) and have been shown to induce tumors in mouse skin. Exxon has developed a new method of refining these materials, a severe hydrotreatment process that is optimized for PAH removal. The specific objectives of the current study were to assess PAH reduction and then to evaluate directly the dermal carcinogenic potential of the materials that spanned the range of products produced by this method. The test samples included unrefined light and heavy vacuum distillates from a naphthenic crude oil, as well as the corresponding severely hydrotreated products. Two sets of samples were prepared to assess the effects of various operating parameters in the reactor. Additionally, positive (benzo[a]pyrene), negative (white mineral oil) and vehicle (toluene) control groups were included to assess the sensitivity and specificity of the bioassay. Each sample was applied in twice-weekly aliquots to the backs of 40 male C3H mice. In the analytical studies, significant reductions in the levels of several specific PAH were demonstrated. In the dermal carcinogenesis studies, the unrefined oils and the positive control induced tumors and also significantly reduced survival. None of the mice treated with severely hydrotreated oils or with the negative or vehicle controls developed skin tumors, and survival of these mice was not significantly different from the control. Thus, the data demonstrated that this new, severe hydrotreatment process was an effective means of converting carcinogenic feedstocks to non-carcinogenic products.

  15. Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Tzu-Yi; Hong, Chwan-Yang [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China); Sasado, Takao [Laboratory of Bioresources, National Institute for Basic Biology, Okazaki (Japan); Kashiwada, Shosaku [Research Center for Life and Environmental Sciences, Department of Life Sciences, the Toyo University, Gunma (Japan); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China)

    2016-01-15

    Highlights: • Propiconazole initiates ROS-induced oxidative stress and damage in medaka fish. • Early life exposure to propiconazole increases incidence of hepatocarcionogensis in p53{sup −/−} medaka. • Oxidative stress and CYP induction involved in p53 regulation are key events in propiconazole-induced hepatotumorigenesis. • Propiconazole-induced toxic response in medaka is compatible with that in rodents. - Abstract: Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53{sup −/−} mutant of medaka fish (Oryzias latipes) to propiconazole (2.5–250 μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53{sup −/−} mutant medaka with early life exposure to propiconazole showed increased incidence of

  16. Formaldehyde in dentistry: a review of mutagenic and carcinogenic potential

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, B.B.; Chestner, S.B.

    1981-09-01

    For many years there has been controversy over the value of antimicrobial drugs for intracanal dressings in endodontics. Formocresol, a formaldehyde compound, has evolved as the preferred drug for routine endodontic procedures, as well as pediatric endodontics. The increase in the use of formaldehyde has been complicated by the introduction of paraformaldehyde pastes for filling root canals. Neither of these formulas has ever been standardized. The doses are arbitrary, and the common dose of formocresol has been shown to be many times greater than the minimum dose needed for effect. The efficacy of paraformaldehyde pastes is questionable and remains clouded by inconclusive evidence, conflicting research, inadequate terminology, and a lack of convincing statistical evidence. The clinical use and delivery of formocresol and paraformaldehyde pastes remain arbitrary and unscientific. Formaldehyde has a known toxic mutagenic and carcinogenic potential. Many investigations have been conducted to measure the risk of exposure to formaldehyde; it is clear that formaldehyde poses a carcinogenic risk in humans. There is a need to reevaluate the rationale underlying the use of formaldehyde in dentistry particularly in light of its deleterious effects.

  17. How well can in vitro data predict in vivo effects of chemicals? Rodent carcinogenicity as a case study.

    Science.gov (United States)

    Anthony Tony Cox, Louis; Popken, Douglas A; Kaplan, A Michael; Plunkett, Laura M; Becker, Richard A

    2016-06-01

    A recent research article by the National Center for Computational Toxicology (NCCT) (Kleinstreuer et al., 2013), indicated that high throughput screening (HTS) data from assays linked to hallmarks and presumed pathways of carcinogenesis could be used to predict classification of pesticides as either (a) possible, probable or likely rodent carcinogens; or (b) not likely carcinogens or evidence of non-carcinogenicity. Using independently developed software to validate the computational results, we replicated the majority of the results reported. We also found that the prediction model correlating cancer pathway bioactivity scores with in vivo carcinogenic effects in rodents was not robust. A change of classification of a single chemical in the test set was capable of changing the overall study conclusion about the statistical significance of the correlation. Furthermore, in the subset of pesticide compounds used in model validation, the accuracy of prediction was no better than chance for about three quarters of the chemicals (those with fewer than 7 positive outcomes in HTS assays representing the 11 histopathological endpoints used in model development), suggesting that the prediction model was not adequate to predict cancer hazard for most of these chemicals. Although the utility of the model for humans is also unclear because a number of the rodent responses modeled (e.g., mouse liver tumors, rat thyroid tumors, rat testicular tumors, etc.) are not considered biologically relevant to human responses, the data examined imply the need for further research with HTS assays and improved models, which might help to predict classifications of in vivo carcinogenic responses in rodents for the pesticide considered, and thus reduce the need for testing in laboratory animals.

  18. Asphalt fume dermal carcinogenicity potential: I. dermal carcinogenicity evaluation of asphalt (bitumen) fume condensates.

    Science.gov (United States)

    Clark, Charles R; Burnett, Donald M; Parker, Craig M; Arp, Earl W; Swanson, Mark S; Minsavage, Gary D; Kriech, Anthony J; Osborn, Linda V; Freeman, James J; Barter, Robert A; Newton, Paul E; Beazley, Shelley L; Stewart, Christopher W

    2011-10-01

    Asphalt (bitumen) fume condensates collected from the headspace above paving and Type III built up roofing asphalt (BURA) tanks were evaluated in two-year dermal carcinogenicity assays in male C3H/HeNCrl mice. A third sample was generated from the BURA using a NIOSH laboratory generation method. Similar to earlier NIOSH studies, the BURA fume condensates were applied dermally in mineral oil twice per week; the paving sample was applied 7 days/week for a total weekly dose of 50 mg/wk in both studies. A single benign papilloma was observed in a group of 80 mice exposed to paving fume condensate at the end of the two-year study and only mild skin irritation was observed. The lab generated BURA fume condensate resulted in statistically significant (P<0.0001) increases in squamous cell carcinomas (35 animals or 55% of animals at risk). The field-matched BURA condensate showed a weaker but significant (P=0.0063) increase (8 carcinomas or 13% of animals) and a longer average latency (90 weeks vs. 76 for the lab fume). Significant irritation was observed in both BURA condensates. It is concluded that the paving fume condensate was not carcinogenic under the test conditions and that the field-matched BURA fume condensate produced a weak tumor response compared to the lab generated sample.

  19. Potential carcinogenicity of homoisoflavanoids and flavonoids from Resina sanguinis draconis (Dracaena cinnabari Balf.).

    Science.gov (United States)

    Vachálková, A; Novotný, L; Nejedlíková, M; Suchý, V

    1995-01-01

    Polarographic behavior of three homoisoflavanoids and four flavanoids isolated from the dragon's blood (Resina sanguinis draconis. Dracaena cinnabari Balf.), collected at Sokotra, was investigated in aprotic solution and an index of potential carcinogenicity tg alpha was determined. Generally, homoisoflavanoids and flavanoids were reduced in two two-electron steps, the first being reversible and the second one irreversible. The parameter tg alpha values indicated that the majority of these compounds possesses no or only marginal potential carcinogenic activity. However, it was demonstrated that some structural modifications in basic flavonoid structure lead to changed electrochemical properties and a substantial increase of derivative potential carcinogenicity.

  20. The prevention of lung cancer induced by a tobacco-specific carcinogen in rodents by green and black Tea.

    Science.gov (United States)

    Chung, F L

    1999-04-01

    A growing body of evidence from studies in laboratory animals indicates that green tea protects against cancer development at various organ sites. We have previously shown that green tea, administered as drinking water, inhibits lung tumor development in A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-l-butanone (NNK), a potent nicotine-derived lung carcinogen found in tobacco. The inhibitory effect of green tea has been attributed to its major polyphenolic compound, epigallocatechin gallate (EGCG), and, to a lesser extent, to caffeine. We have also demonstrated that while levels of O6-methylguanine, a critical lesion in NNK lung tumorigenesis, were not affected in lung DNA. However, the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, were significantly suppressed in mice treated with green tea or EGCG. These studies underscore the importance of the antioxidant activity of green tea and EGCG for their inhibitory activity against lung tumorigenesis. Unlike green tea, the effect of black tea on carcinogenesis has been scarcely studied, even though the worldwide production and consumption of black tea far exceeds that of green tea. The oxidation products found in black tea, thearubigins and theaflavins, also possess antioxidant activity, suggesting that black tea may also inhibit NNK-induced lung tumorigenesis. Indeed, bioassays in A/J mice have shown that black tea given as drinking water retarded the development of lung cancer caused by NNK. However, data on the relationship of black tea consumption with the lung cancer risk in humans are limited and inconclusive. There is a need for additional tumor bioassays in animal models to better examine the protective role of black tea against lung cancer. The development of adenocarcinomas and adenosquamous carcinomas in F344 rats upon chronic administration of NNK provides an important and relevant model for lung carcinogenesis in smokers. Thus far, no information was previously

  1. Species difference among experimental rodents in the activity and induction of cytochrome P-450 isozymes for mutagenic activation of carcinogenic aromatic amines.

    Science.gov (United States)

    Degawa, M; Agatsuma, T; Hashimoto, Y

    1990-12-01

    The expressions of hepatic microsomal cytochrome P-450 isozymes in male rats, mice, hamsters and guinea pigs were studied comparatively with or without an ip injection of a cytochrome P-450 inducer. The activity and quantity of microsomal cytochrome P-450 isozymes were determined respectively by a bacterial mutation assay with Salmonella typhimurium TA98 and immunochemical assays using monoclonal antibodies against rat cytochrome P-450 isozymes. 3-Methoxy-4-aminoazobenzene (3-MeO-AAB), 2-amino-3-methyl-9H-pyrido[2,3-b]indole acetate (MeA alpha C) and 3-methylcholanthrene were used as cytochrome P-450 inducers, and 7 carcinogenic aromatic amines including 3-MeO-AAB and MeA alpha C were used as substrates for the mutation assay. By means of these assays, we examined the species differences among rodents in the activity and induction rate of hepatic cytochrome P-450 isozymes responsible for the mutagenic activation of carcinogenic aromatic amines.

  2. An Evaluation of the Human Carcinogenic Potential of Ethylene Glycol Butyl Ether (Egbe)

    Science.gov (United States)

    This position paper, An Evaluation of the Human Carcinogenic Potential of Ethylene Glycol Butyl Ether, was developed in support of the EPA's evaluation of a petition from the American Chemistry Council requesting to delist EGBE per the Clean Air Act Amendments (CAAA), Titl...

  3. Biotin-mediated epigenetic modifications: Potential defense against the carcinogenicity of benzo[a]pyrene.

    Science.gov (United States)

    Xia, Bo; Pang, Li; Zhuang, Zhi-xiong; Liu, Jian-jun

    2016-01-22

    Environmental pollution and an unhealthy lifestyle result in direct exposure to dangerous chemicals that can modify endogenous pathways and induce malignant transformation of human cells. Although the molecular mechanisms of tumorigenesis are still not well understood, epigenetic alteration may be associated with exogenous chemical-induced carcinogenicity. Given the association between nutrition and cancer, nutrient supplementation may reduce aberrant epigenetic modifications induced by chemicals, thus decreasing carcinogenesis. This paper provides an overview of the epigenetic events caused by benzo[a]pyrene, a procarcinogenic and environmental pollutant, and biotin, an essential water-soluble vitamin, and investigates potential connections between them. This paper also discusses the potential inhibitory effect of biotin-related epigenetic modifications on the carcinogenicity of benzo[a]pyrene. The effect of nutritional supplementation on tumorigenesis involving epigenetic modifications is also discussed.

  4. Mechanism-Based Classification of PAH Mixtures to Predict Carcinogenic Potential.

    Science.gov (United States)

    Tilton, Susan C; Siddens, Lisbeth K; Krueger, Sharon K; Larkin, Andrew J; Löhr, Christiane V; Williams, David E; Baird, William M; Waters, Katrina M

    2015-07-01

    We have previously shown that relative potency factors and DNA adduct measurements are inadequate for predicting carcinogenicity of certain polycyclic aromatic hydrocarbons (PAHs) and PAH mixtures, particularly those that function through alternate pathways or exhibit greater promotional activity compared to benzo[a]pyrene (BaP). Therefore, we developed a pathway-based approach for classification of tumor outcome after dermal exposure to PAH/mixtures. FVB/N mice were exposed to dibenzo[def,p]chrysene (DBC), BaP, or environmental PAH mixtures (Mix 1-3) following a 2-stage initiation/promotion skin tumor protocol. Resulting tumor incidence could be categorized by carcinogenic potency as DBC > BaP = Mix2 = Mix3 > Mix1 = Control, based on statistical significance. Gene expression profiles measured in skin of mice collected 12 h post-initiation were compared with tumor outcome for identification of short-term bioactivity profiles. A Bayesian integration model was utilized to identify biological pathways predictive of PAH carcinogenic potential during initiation. Integration of probability matrices from four enriched pathways (P < .05) for DNA damage, apoptosis, response to chemical stimulus, and interferon gamma signaling resulted in the highest classification accuracy with leave-one-out cross validation. This pathway-driven approach was successfully utilized to distinguish early regulatory events during initiation prognostic for tumor outcome and provides proof-of-concept for using short-term initiation studies to classify carcinogenic potential of environmental PAH mixtures. These data further provide a 'source-to-outcome' model that could be used to predict PAH interactions during tumorigenesis and provide an example of how mode-of-action-based risk assessment could be employed for environmental PAH mixtures.

  5. Potential health effects of exposure to carcinogenic compounds in incense smoke in temple workers.

    Science.gov (United States)

    Navasumrit, Panida; Arayasiri, Manasawee; Hiang, Ohmar May Tin; Leechawengwongs, Manoon; Promvijit, Jeerawan; Choonvisase, Suppachai; Chantchaemsai, Samroeng; Nakngam, Netnapa; Mahidol, Chulabhorn; Ruchirawat, Mathuros

    2008-05-09

    Incense smoke is a potential hazard to human health due to various airborne carcinogens emitted from incense burning. This study aimed to evaluate the potential health effects of exposure to benzene, 1,3-butadiene, and polycyclic aromatic hydrocarbons (PAHs) emitted from incense smoke in temple workers. Exposure and health risks were assessed through the measurement of ambient exposure as well as through the use of biomarkers of exposure and early biological effects. Ambient air measurement showed that incense burning generates significantly higher levels of airborne benzene (Pincense burning may increase health risk for the development of cancer in temple workers.

  6. Potentially mutagenic impurities: analysis of structural classes and carcinogenic potencies of chemical intermediates in pharmaceutical syntheses supports alternative methods to the default TTC for calculating safe levels of impurities.

    Science.gov (United States)

    Galloway, Sheila M; Vijayaraj Reddy, M; McGettigan, Katherine; Gealy, Robert; Bercu, Joel

    2013-08-01

    Potentially mutagenic impurities in new pharmaceuticals are controlled to levels with negligible risk, the TTC (threshold of toxicological concern, 1.5 μg/day for a lifetime). The TTC was based on the more potent rodent carcinogens, excluding the highly potent "cohort of concern" (COC; for mutagenic carcinogens these are N-nitroso, Aflatoxin-like, and azoxy structures). We compared molecules with DEREK "structural alerts" for mutagenicity used in drug syntheses with the mutagenic carcinogens in the Gold Carcinogenicity Potency Database. Data from 108 diverse synthetic routes from 13 companies confirm that many "alerting" or mutagenic chemicals are in structural classes with lower carcinogenic potency than those used to derive the TTC. Acceptable daily intakes can be established that are higher than the default TTC for many structural classes (e.g., mono-functional alkyl halides and certain aromatic amines). Examples of ADIs for lifetime and shorter-term exposure are given for chemicals of various potencies. The percentage of chemicals with DEREK alerts that proved mutagenic in the Ames test ranged from 36% to 83%, depending on structural class, demonstrating that such SAR analysis to "flag" potential mutagens is conservative. We also note that aromatic azoxy compounds need not be classed as COC, which was based on alkyl azoxy chemicals.

  7. Potential health risks related to carcinogens in the atmospheric environment in India.

    Science.gov (United States)

    Gurjar, B R; Mohan, M; Sidhu, K S

    1996-10-01

    In India, rapid urbanization and industrialization have contributed positively toward meeting the materialistic needs of the citizens, but have also resulted in contamination of the atmospheric environment. This paper deals with the assessment of potential health risks posed by carcinogenic substances, namely cadmium, chromium, and nickel, present in certain atmospheric environments in India. Average air concentrations of these carcinogenic metals have been assessed for different states and regions of India (C. R. Krishnamurti and P. Vishwanathan, Toxic Metals in the Indian Environment, Tata/McGraw-Hill, New Delhi, 1991). Based on these assessments, both individual and societal risks have been estimated in different states of the country, and comparisons were made. Reported concentration, release sources, potential health risks including cancer risk estimates, and ambient air interim guidelines are discussed. The reported environmental releases and cancer risk from cadmium are minimal. There is a potential for increased respiratory cancer risk from exposure to chromium and nickel in some northern Indian states. These metals are irritants to nasal passages and the respiratory tract. Chromium is also corrosive to mucus membranes. They have the potential to cause chronic respiratory problems. Since it appears that these metals may cause some adverse health effects in humans, exposure to these ambient air pollutants should be minimized by managing the release of these contaminants to the environment. There is a need for the development and strict enforcement of national and state regulatory standards.

  8. Prevalence of genotoxic chemicals among animal and human carcinogens evaluated in the IARC Monograph Series.

    Science.gov (United States)

    Bartsch, H; Malaveille, C

    1989-06-01

    To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the IARC Monographs for their carcinogenic effects in humans and animals and for the activity in short-term genotoxicity tests. The prevalence of genotoxic carcinogens on four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and on agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 149) was determined. A high prevalence in the order of 80 to 90% of genotoxic carcinogens was found in each of the groups 1, 2A and 2B, which were also shown to be multi-species/multi-tissues carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and 3. The results of this analysis indicate that (a) an agent with unknown carcinogenic potential showing sufficient evidence of activity in in vitro/in vivo genotoxicity assays (involving as endpoints DNA damage and chromosomal/mutational damage) may represent a hazard to humans; and b) an agent showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity by rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens. Overall, this analysis implies that genotoxic carcinogens add more to the cancer burden in man than non-genotoxic carcinogens. Thus, identification of such genotoxic carcinogens and subsequent lowering of exposure will remain the main goal for primary cancer prevention in man.

  9. JaCVAM-organized international validation study of the in vivo rodent alkaline comet assay for the detection of genotoxic carcinogens: I. Summary of pre-validation study results.

    Science.gov (United States)

    Uno, Yoshifumi; Kojima, Hajime; Omori, Takashi; Corvi, Raffaella; Honma, Masamistu; Schechtman, Leonard M; Tice, Raymond R; Burlinson, Brian; Escobar, Patricia A; Kraynak, Andrew R; Nakagawa, Yuzuki; Nakajima, Madoka; Pant, Kamala; Asano, Norihide; Lovell, David; Morita, Takeshi; Ohno, Yasuo; Hayashi, Makoto

    2015-07-01

    The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this validation effort was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The purpose of the pre-validation studies (i.e., Phase 1 through 3), conducted in four or five laboratories with extensive comet assay experience, was to optimize the protocol to be used during the definitive validation study.

  10. The Food and Beverage Occurrence of Furfuryl Alcohol and Myrcene—Two Emerging Potential Human Carcinogens?

    Directory of Open Access Journals (Sweden)

    Alex O. Okaru

    2017-03-01

    Full Text Available For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The World Health Organization (WHO International Agency for Research on Cancer (IARC continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene are potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages, while β-myrcene occurs naturally as a constituent of the essential oils of plants such as hops, lemongrass, and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using literature review data. Additionally, results of furfuryl alcohol occurrence from our own nuclear magnetic resonance (NMR analysis are included. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg and in some fish products (about 10 mg/kg, while among beverages, wines contained between 1 and 10 mg/L, with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

  11. [Experimental study on the potential carcinogenicity of cooking oil fume condensate].

    Science.gov (United States)

    Zhao, Jinming; Su, Fei; Zhou, Shaoqin

    2002-02-01

    The potential carcinogenicity of cooking oil fume condensate (COFC) to human was studied. Human embryo lung diploid fibroblast cell strain KMB-17 cell was applied to establish a human diploid cell transformation system in vitro. Different concentrations of COFC were added into the media and co-incubated with cells. The malignant degree of transformation was assessed by the biological characteristics of the cells. The concentrations of COFC within the dose range of the experiment could induce the malignant transformation of KMB-17 cell, and with a obvious dose-response relationship (r = 0.9811). Transformed cells have exhibited many characteristics associating with malignant transformation, such as loss of density and contact-dependent inhibition, growth at low serum concentration, agglutination by low concentration of Con A, alteration of karyotype from diploid to aneuploid, and lose of anchorage dependence. It suggested that the malignant transformation of human embryo lung diploid fibroblast cell strain KMB-17 cell could be induced by COFC, which might have potential carcinogenicity to human.

  12. Assessment of the mutagenic, recombinagenic and carcinogenic potential of orlistat in somatic cells of Drosophila melanogaster.

    Science.gov (United States)

    Orsolin, P C; Silva-Oliveira, R G; Nepomuceno, J C

    2012-08-01

    In this study the mutagenic, recombinagenic, carcinogenic and anticarcinogenic potential of orlistat was assessed using the somatic mutation and recombination test (SMART) and the epithelial tumor detection test (wts). The experiments were conducted on Drosophila melanogaster. In the assessment using SMART, larvae, descendants from the standard (ST) cross and the high bioactivation (HB) cross, were treated chronically with three orlistat concentrations. The results revealed a recombinagenic effect, associated with orlistat, in the descendants of the HB cross, at all three levels of concentration. Homologous recombination can function as a determinant at different stages of carcinogenesis. For verification, larvae from the wts test, descendants of the wts/TM3 virgin female and mwh/mwh male cross, were treated with the same three orlistat concentrations separately and in association with mitomicin C (0.1mM). The results did not, however, provide evidence that orlistat has carcinogenic potential nor was it associated with the reduction of tumors induced by mitomicin C in D. melanogaster.

  13. Gaps in scientific knowledge about the carcinogenic potential of asphalt/bitumen fumes.

    Science.gov (United States)

    Schulte, Paul A

    2007-01-01

    Despite a relatively large body of published research, the potential carcinogenicity of asphalt/bitumen fumes is still a vexing question. Various uncertainties and gaps in scientific knowledge need to be addressed. These include uncertainties in chemistry, animal studies, and human studies. The chemistry of asphalt/bitumen fumes is complex and varies according to the source of the crude oil and the application parameters. The epidemiological studies, while showing weak evidence of lung cancer, are inconsistent and many confounding factors have not been addressed. Studies of animal exposure are also inconsistent regarding laboratory and field-generated fumes. There is a need for further human studies that address potential confounding factors such as smoking, diet, coal tar, and diesel exposures. Animal inhalation studies need to be conducted with asphalt/bitumen fumes that are chemically representative of roofing and paving fumes. Underlying all of this is the need for continued characterization of fumes so their use in animal and field studies can be properly assessed. Nonetheless, uncertainties such as these should not preclude appropriate public health actions to protect workers in the even that asphalt fumes are found to be a carcinogenic hazard.

  14. Automobile tires--a potential source of highly carcinogenic dibenzopyrenes to the environment.

    Science.gov (United States)

    Sadiktsis, Ioannis; Bergvall, Christoffer; Johansson, Christer; Westerholm, Roger

    2012-03-20

    Eight tires were analyzed for 15 high molecular weight (HMW) polycyclic aromatic hydrocarbons (PAH), using pressurized fluid extraction. The variability of the PAH concentrations determined between different tires was large; a factor of 22.6 between the lowest and the highest. The relative abundance of the analytes was quite similar regardless of tire. Almost all (92.3%) of the total extractable PAH content was attributed to five PAHs: benzo[ghi]perylene, coronene, indeno[1,2,3-cd]pyrene, benzo[e]pyrene, and benzo[a]pyrene. The difference in the measured PAH content between summer and winter tires varied substantially across manufacturers, making estimates of total vehicle fleet emissions very uncertain. However, when comparing different types of tires from the same manufacturer they had significantly (p = 0.05) different PAH content. Previously, there have been no data available for carcinogenic dibenzopyrene isomers in automobile tires. In this study, the four dibenzopyrene isomers dibenzo[a,l]pyrene, dibenzo[a,e]pyrene, dibenzo[a,i]pyrene, and dibenzo[a,h]pyrene constituted automobile tires may be a potential previously unknown source of carcinogenic dibenzopyrenes to the environment.

  15. 7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic metabolites of pyrrolizidine alkaloids.

    Science.gov (United States)

    He, Xiaobo; Xia, Qingsu; Fu, Peter P

    2017-04-03

    Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Metabolism of PAs in vivo generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed to be responsible for PA-induced liver tumor formation in rats. In this present study, we determined that the same set of DHP-DNA adducts was formed upon the incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7-cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor formation.

  16. International Conference on Harmonisation: guidance on testing for carcinogenicity of pharmaceuticals. Notice. Food and Drug Administration, HHS.

    Science.gov (United States)

    1998-02-23

    The Food and Drug Administration (FDA) is publishing a guidance entitled "S1B Testing for Carcinogenicity of Pharmaceuticals." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance outlines experimental approaches to evaluating the carcinogenic potential of pharmaceuticals to humans that may obviate the necessity for the routine conduct of two long-term rodent carcinogenicity studies

  17. Quantitative comparison between in vivo DNA adduct formation from exposure to selected DNA-reactive carcinogens, natural background levels of DNA adduct formation and tumour incidence in rodent bioassays.

    Science.gov (United States)

    Paini, Alicia; Scholz, Gabriele; Marin-Kuan, Maricel; Schilter, Benoît; O'Brien, John; van Bladeren, Peter J; Rietjens, Ivonne M C M

    2011-09-01

    This study aimed at quantitatively comparing the occurrence/formation of DNA adducts with the carcinogenicity induced by a selection of DNA-reactive genotoxic carcinogens. Contrary to previous efforts, we used a very uniform set of data, limited to in vivo rat liver studies in order to investigate whether a correlation can be obtained, using a benchmark dose (BMD) approach. Dose-response data on both carcinogenicity and in vivo DNA adduct formation were available for six compounds, i.e. 2-acetylaminofluorene, aflatoxin B1, methyleugenol, safrole, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and tamoxifen. BMD(10) values for liver carcinogenicity were calculated using the US Environmental Protection Agency BMD software. DNA adduct levels at this dose were extrapolated assuming linearity of the DNA adduct dose response. In addition, the levels of DNA adducts at the BMD(10) were compared to available data on endogenous background DNA damage in the target organ. Although for an individual carcinogen the tumour response increases when adduct levels increase, our results demonstrate that when comparing different carcinogens, no quantitative correlation exists between the level of DNA adduct formation and carcinogenicity. These data confirm that the quantity of DNA adducts formed by a DNA-reactive compound is not a carcinogenicity predictor but that other factors such as type of adduct and mutagenic potential may be equally relevant. Moreover, comparison to background DNA damage supports the notion that the mere occurrence of DNA adducts above or below the level of endogenous DNA damage is neither correlated to development of cancer. These data strongly emphasise the need to apply the mode of action framework to understand the contribution of other biological effect markers playing a role in carcinogenicity.

  18. Screening assays for carcinogenic agents and mixtures: an appraisal based on data in the IARC Monograph series.

    Science.gov (United States)

    Bartsch, H; Malaveille, C

    1990-01-01

    To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans and which types of short-term test are more relevant for predicting human hazards, an analysis was performed on agents that were evaluated in IARC Monographs Supplements 6 and 7 for their carcinogenic effects in humans and animals and for activity in short-term genotoxicity tests. The prevalence of genotoxicity among four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 66) was determined. Each of the groups 1, 2A and 2B contained a high proportion (80-90%) of genotoxic carcinogens, which were also multi-species or multi-tissue carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and many in group 3. Although limited by the data-base available through the Monographs series, this analysis implies that genotoxic carcinogens add more to the human cancer burden than non-genotoxic carcinogens. Thus, the continued use of in vitro/in vivo short-term tests, involving as endpoints DNA chromosomal or mutational damage, to identify genotoxic carcinogens or in the isolation of carcinogenic components in complex mixtures is fully justified. It is concluded that (a) an agent or complex mixture with unknown carcinogenic potential showing sufficient evidence of activity in genotoxicity assays in vitro or in vivo is likely to represent a hazard to humans and (b) an agent or complex mixture showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity for rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens.

  19. Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

    NARCIS (Netherlands)

    Kuempel, Eileen D; Jaurand, Marie-Claude; Møller, Peter; Morimoto, Yasuo; Kobayashi, Norihiro; Pinkerton, Kent E; Sargent, Linda M; Vermeulen, Roel C H; Fubini, Bice; Kane, Agnes B

    2017-01-01

    In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the

  20. 29 CFR 1990.131 - Priority lists for regulating potential occupational carcinogens.

    Science.gov (United States)

    2010-07-01

    ... List. The inclusion or exclusion of any substance on these lists shall not be subject to judicial... carcinogen which has not been placed on these lists. The inclusion of a substance on either of these...

  1. PKC-mediated potentiation of morphine analgesia by St. John's Wort in rodents and humans.

    Science.gov (United States)

    Galeotti, Nicoletta; Farzad, Mersedeh; Bianchi, Enrica; Ghelardini, Carla

    2014-01-01

    Our purpose was to combine the use of morphine with clinically available inhibitors of protein kinase C (PKC), finally potentiating morphine analgesia in humans. Thermal tests were performed in rodents and humans previously administered with acute or chronic morphine combined or not with increasing doses of the PKC-blocker St. John's Wort (SJW) or its main component hypericin. Phosphorylation of the γ subunit of PKC enzyme was assayed by western blotting in the periaqueductal grey matter (PAG) from rodents co-administered with morphine and hypericin and was prevented in rodent PAG by SJW or hypericin co-administration with morphine, inducing a potentiation of morphine analgesia in thermal pain. The score of pain assessment in healthy volunteers were decreased by 40% when morphine was co-administered with SJW at a dose largely below those used to obtain an antidepressant or analgesic effect in both rodents and humans. The SJW/hypericin potentiating effect lasted in time and preserved morphine analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW could reduce the dose of morphine obtaining the same analgesic effect. Therefore, SJW and one of its main components, hypericin, appear ideal to potentiate morphine-induced analgesia.

  2. Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia.

    Directory of Open Access Journals (Sweden)

    Michael J Smout

    2015-10-01

    Full Text Available Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA. Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world.

  3. The potential carcinogenic risk of tanning beds: clinical guidelines and patient safety advice

    Directory of Open Access Journals (Sweden)

    Mette Mogensen

    2010-10-01

    Full Text Available Mette Mogensen1, Gregor BE Jemec21Department of Dermatology, Gentofte Hospital, Hellerup, Denmark; 2Department of Dermatology, Roskilde Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, DenmarkIntroduction: In 2009, the WHO listed ultraviolet (UV radiation as a group 1 carcinogen. In spite of this, each year, millions of people tan indoor in Western countries. The aim of this review is to summarize evidence of tanning bed carcinogenesis and to present guidelines for use of tanning beds and patient safety advice.Methods: A narrative review of the literature was conducted based on both PubMed and Medline searches and on literature review of the retrieved papers.Results: Use of indoor tanning beds represents a significant and avoidable risk factor for the development of both melanoma and nonmelanoma skin cancers. Frequent tanners are more often adolescent females. Tanning beds have additional potential adverse effects such as burns, solar skin damage, infection, and possibly also addictive behavior.Discussion: The effort in preventing UV light-induced carcinogenesis should currently be aimed at developing new strategies for public health information. Tanning beds are one preventable source of UV radiation. In the majority of people solar UV radiation continues to be the major factor and therefore anti-tanning campaigns must always include sunbathers.Keywords: tanning beds, skin cancers, melanoma, nonmelanoma

  4. Prediction of the carcinogenic potential of human pharmaceuticals using repeated dose toxicity data and their pharmacological properties

    Directory of Open Access Journals (Sweden)

    Jan Willem Van Der Laan

    2016-10-01

    properties of compounds in relation to potential class-effects, both in the negative and positive direction. A high negative and a high positive predictivity will both result in waiving the need for conducting 2-year rat carcinogenicity studies, if this is accepted by Regulatory Authorities, which will save , large numbers of animals, reduce drug development

  5. The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report

    Directory of Open Access Journals (Sweden)

    Vetter Claudia S

    2006-01-01

    Full Text Available Abstract Background Since tacrolimus ointment was approved by the U.S. Food and Drug Administration (FDA as a promising treatment for atopic dermatitis, it has been approved in more than 30 additional countries, including numerous European Union member nations. Moreover, in the current clinical routine the use of this drug is no longer restricted to the approved indication, but has been extended to a wide variety of inflammatory skin diseases including some with the potential of malignant transformation. So far, the side-effects reported from the topical use of tacrolimus have been relatively minor (e.g. burning, pruritus, erythema. Recently, however, the FDA reviewed the safety of topical tacrolimus, which resulted in a warning that the use of calcineurin inhibitors may be associated with an increased risk of cancer. Case presentation Oral lichen planus (OLP was diagnosed in a 56-year-old women in February 1999. After several ineffective local and systemic therapeutic measures an off-label treatment of this recalcitrant condition using Tacrolimus 0.1% ointment was initiated in May 2002. After a few weeks of treatment most of the lesions ameliorated, with the exception of the plaques on the sides of the tongue. Nevertheless, the patient became free of symptoms which, however, reoccurred once tacrolimus was weaned, as a consequence treatment was maintained. In April 2005, the plaques on the left side of the tongue appeared increasingly compact and a biopsy specimen confirmed the suspected diagnosis of an oral squamous cell carcinoma. Conclusion The suspected causal relationship between topical use of tacrolimus and the development of a squamous cell carcinoma prompted us to test the notion that the carcinogenicity of tacrolimus may go beyond mere immune suppression. To this end, tacrolimus has been shown to have an impact on cancer signalling pathways such as the MAPK and the p53 pathway. In the given case, we were able to demonstrate that these

  6. A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment.

    Science.gov (United States)

    Williams, Gary M; Aardema, Marilyn; Acquavella, John; Berry, Sir Colin; Brusick, David; Burns, Michele M; de Camargo, Joao Lauro Viana; Garabrant, David; Greim, Helmut A; Kier, Larry D; Kirkland, David J; Marsh, Gary; Solomon, Keith R; Sorahan, Tom; Roberts, Ashley; Weed, Douglas L

    2016-09-01

    The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.

  7. Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

    DEFF Research Database (Denmark)

    Kuempel, Eileen D.; Jaurand, Marie-Claude; Møller, Peter

    2017-01-01

    In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based...... on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting...... in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials...

  8. A review of mammalian carcinogenicity study design and potential effects of alternate test procedures on the safety evaluation of food ingredients.

    Science.gov (United States)

    Hayes, A W; Dayan, A D; Hall, W C; Kodell, R L; Williams, G M; Waddell, W D; Slesinski, R S; Kruger, C L

    2011-06-01

    Extensive experience in conducting long term cancer bioassays has been gained over the past 50 years of animal testing on drugs, pesticides, industrial chemicals, food additives and consumer products. Testing protocols for the conduct of carcinogenicity studies in rodents have been developed in Guidelines promulgated by regulatory agencies, including the US EPA (Environmental Protection Agency), the US FDA (Food and Drug Administration), the OECD (Organization for Economic Co-operation and Development) for the EU member states and the MAFF (Ministries of Agriculture, Forestries and Fisheries) and MHW (Ministry of Health and Welfare) in Japan. The basis of critical elements of the study design that lead to an accepted identification of the carcinogenic hazard of substances in food and beverages is the focus of this review. The approaches used by entities well-known for carcinogenicity testing and/or guideline development are discussed. Particular focus is placed on comparison of testing programs used by the US National Toxicology Program (NTP) and advocated in OECD guidelines to the testing programs of the European Ramazzini Foundation (ERF), an organization with numerous published carcinogenicity studies. This focus allows for a good comparison of differences in approaches to carcinogenicity testing and allows for a critical consideration of elements important to appropriate carcinogenicity study designs and practices. OECD protocols serve as good standard models for carcinogenicity testing protocol design. Additionally, the detailed design of any protocol should include attention to the rationale for inclusion of particular elements, including the impact of those elements on study interpretations. Appropriate interpretation of study results is dependent on rigorous evaluation of the study design and conduct, including differences from standard practices. Important considerations are differences in the strain of animal used, diet and housing practices, rigorousness

  9. The Therapeutic Potential of Induced Pluripotent Stem Cells After Stroke: Evidence from Rodent Models.

    Science.gov (United States)

    Zents, Karlijn; Copray, Sjef

    2016-01-01

    Stroke is the second most common cause of death and the leading cause of disability in the world. About 30% of the people that are affected by stroke die within a year; 25% of the patients that survive stroke remain in need of care after a year. Therefore, stroke is a major burden for health care costs. The most common subtype is ischemic stroke. This type is characterized by a reduced and insufficient blood supply to a certain part of the brain. Despite the high prevalence of stroke, the currently used therapeutic interventions are limited. No therapies that aim to restore damaged neuronal tissue or to promote recovery are available nowadays. Transplantation of stem cell-derived cells has been investigated as a potential regenerative and protective treatment. Embryonic stem cell (ESC)-based cell therapy in rodent models of stroke has been shown to improve functional outcome. However, the clinical use of ESCs still raises ethical questions and implantation of ESC-derived cells requires continuous immunosuppression. The groundbreaking detection of induced pluripotent stem cells (iPSCs) has provided a most promising alternative. This mini-review summarizes current literature in which the potential use of iPSC-derived cells has been tested in rodent models of stroke. iPSC-based cell therapy has been demonstrated to improve motor function, decrease stroke volume, promote neurogenesis and angiogenesis and to exert immunomodulatory, anti-inflammatory effects in the brain of stroke-affected rodents.

  10. Studies on the Mutagenicity and Teratogenicity of Kuianchun and Its Potential Carcinogenicity Prediction

    Institute of Scientific and Technical Information of China (English)

    LIANG Jian-ping; ZHANG Li; CAO Sui-zhong; ZHOU Li-xia; ZHOU Xue-hui; LIU Zong-ping; WEI Chun-mei; MIAO Xiao-lin; WEI Zeng-quan

    2002-01-01

    Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus test and sperm abnormality test, to detect the mutagenicity of Kuianchun. The carcinogenicity prediction and battery selection method (CPBS method) was used to determine the probability of carcinogenicity of Kuianchun based upon the results of shortterm tests mentioned above. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. In Ames test, Kuianchun showed mutagenic for Salmonella typhimurium strains TA98 and TA100 in the absence and presence of microsomal metabolic activation system (S9-mix). However, the mutagenicity was reduced by the addition of S9-mix. In micronucleus test, Kuianchun was administered intra-peritoneally to male mouse 30 hours and 6 hours before they were killed respectively. The result indicated that there was no significant difference on the number of micronucleated polychromatic erythrocytes (PCEs) in the mouse bone marrow induced by Kuianchun compared with the negative contrast (50% DMSO) (P > 0.05). In sperm abnormality test, Kuianchun was administered through a gastric incubation to male mouse as a suspension in 2% Tween-80. The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnormal sperms induced by Kuianchun was not significant compared with the negative contrast (P>0.05). In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1/30,1/20 and 1/15 LDs0 during 6 - 15days of pregnancy period (the LD50 = 9000mg/kg). No toxicity was found either on mother and embryo in mouse, and teratogenic effects were also not observed at all tested dosages. The probability of carcinogenicity of Kuianchun is 23.8 % (θ = 0.238). The result demonstrated that Kuianchun is a non-carcinogen.

  11. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chun-Hung [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China); Chou, Pei-Hsin [Department of Environmental Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China)

    2014-07-30

    Highlights: • We assess ecotoxicological impact of azole fungicides in the aquatic environment. • Carcinogenic and non-carcinogenic azoles show different CYP activities in medaka. • We compare azole-induced CYP expression and carcinogenesis between fish and rodents. • Liver CYP-enzyme induction is a key event in conazole-induced tumorigenesis. • We suggest toxicity evaluation methods for azole fungicides using medaka fish. - Abstract: Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish

  12. In vitro screening of inhibition of PPAR-γ activity as a first step in identification of potential breast carcinogens

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov; Lundqvist, J.; Petersen, R. K.

    2015-01-01

    Alcohol consumption and increased estrogen levels are major risk factors for breast cancer, and peroxisome proliferator-activated receptor γ (PPAR-γ) plays an important role in alcohol-induced breast cancer. PPAR-γ activity is inhibited by ethanol, leading to increased aromatase activity...... and estrogen biosynthesis ultimately leading to breast cancer. If other organic solvents inhibit PPAR-γ activity, they should also lead to increased oestrogen biosynthesis and thus be potential breast carcinogens. Ten commonly used hydrophilic organic solvents were first tested in a cell-based screening assay...

  13. Ferns and lycopods--a potential treasury of anticancer agents but also a carcinogenic hazard.

    Science.gov (United States)

    Tomšík, Pavel

    2014-06-01

    Many species of seedless vascular plants-ferns and lycopods-have been used as food and folk medicine since ancient times. Some of them have become the focus of intensive research concerning their anticancer properties. Studies on the anticancer effect of crude extracts are being increasingly replaced by bioactivity-guided fractionation, as well as detailed assessment of the mechanism of action. Numerous compounds-especially flavonoids such as amentoflavone and protoapigenone, and also simpler phenolic compounds, steroids, alkaloids and terpenoids-were isolated and found to be cytotoxic, particularly pro-apoptotic, or to induce cell cycle arrest in cancer cell lines in vitro. In in vivo experiments, some fern-derived compounds inhibited tumour growth with little toxicity. On the other hand, many ferns-not only the well-known Bracken (Pteridium)-may pose a significant hazard to human health due to the fact that they contain carcinogenic sesquiterpenoids and their analogues. The objective of this review is to summarise the recent state of research on the anticancer properties of ferns and lycopods, with a focus on their characteristic bioactive constituents. The carcinogenic hazard posed by ferns is also mentioned.

  14. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish.

    Science.gov (United States)

    Lin, Chun-Hung; Chou, Pei-Hsin; Chen, Pei-Jen

    2014-07-30

    Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish populations in the aquatic environment.

  15. Immunocontraceptive potential of recombinantly expressed minimized chicken riboflavin carrier protein (mini-RCP) in rodents.

    Science.gov (United States)

    Subramanian, Sarada; Karandeb, Anjali A; Adiga, P Radhakantha

    2004-12-01

    Chicken riboflavin carrier protein (RCP; 219 AA) harbours four linear epitopes, constituted by the peptide residues 3-23, 64-83, 130-147 and 200-219. Antibodies to these sequences bioneutralize maternal RCP and provide protection from pregnancy in rodents. In order to overcome the major histocompatibility complex-dependent variability in immune response often encountered with use of single peptides for vaccination in genetically outbred populations, we have assembled a novel synthetic gene, incorporating in tandem the nucleotide sequences coding for all the four neutralizing epitopes of chicken RCP and expressed in Escherichia coli. The gene product, mini-RCP has been characterized for its immunogenic properties and contraceptive potential in rodents. Immunization of rabbits and rats led to generation of antibodies against individual peptide components, as determined by enzyme-linked-immunosorbent assay (ELISA). However, immunized rats carried pregnancy to term and delivered healthy offsprings. Antisera from these rats exhibited decreased affinity of binding to the native protein. These findings suggest that the prospects of covalently-linked epitope peptides need to be cautiously evaluated during the design and development of peptide-based vaccines.

  16. Results of the International Validation of the in vivo rodent alkaline comet assay for the detection of genotoxic carcinogens: Individual data for 1,2-dibromoethane, p-anisidine, and o-anthranilic acid in the 2nd step of the 4th phase Validation Study under the JaCVAM initiative.

    Science.gov (United States)

    Takasawa, Hironao; Takashima, Rie; Narumi, Kazunori; Kawasako, Kazufumi; Hattori, Akiko; Kawabata, Masayoshi; Hamada, Shuichi

    2015-07-01

    As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative International Validation Study of an in vivo rat alkaline comet assay, we examined 1,2-dibromoethane (DBE), p-anisidine (ASD), and o-anthranilic acid (ANT) to investigate the effectiveness of the comet assay in detecting genotoxic carcinogens. Each of the three test chemicals was administered to 5 male Sprague-Dawley rats per group by oral gavage at 48, 24, and 3h before specimen preparation. Single cells were collected from the liver and glandular stomach at 3h after the final dosing, and the specimens prepared from these two organs were subjected to electrophoresis under alkaline conditions (pH>13). The percentage of DNA intensity in the comet tail was then assessed using an image analysis system. A micronucleus (MN) assay was also conducted using these three test chemicals with the bone marrow (BM) cells collected from the same animals simultaneously used in the comet assay, i.e., combination study of the comet assay and BM MN assay. A genotoxic (Ames positive) rodent carcinogen, DBE gave a positive result in the comet assay in the present study, while a genotoxic (Ames positive) non-carcinogen, ASD and a non-genotoxic (Ames negative) non-carcinogen, ANT showed negative results in the comet assay. All three chemicals produced negative results in the BM MN assay. While the comet assay findings in the present study were consistent with those obtained from the rodent carcinogenicity studies for the three test chemicals, we consider the positive result in the comet assay for DBE to be particularly meaningful, given that this chemical produced a negative result in the BM MN assay. Therefore, the combination study of the comet assay and BM MN assay is a useful method to detect genotoxic carcinogens that are undetectable with the BM MN assay alone.

  17. Exposure of mouse skin to organic peroxides: subchronic effects related to carcinogenic potential.

    Science.gov (United States)

    Hanausek, Margaret; Walaszek, Zbigniew; Viaje, Aurora; LaBate, Michael; Spears, Erick; Farrell, David; Henrich, Richard; Tveit, Ann; Walborg, Earl F; Slaga, Thomas J

    2004-03-01

    . Neither TBPB nor TBIBHP produced detectable mutations in the c-Ha-ras protooncogene, indicating that they are not likely to possess tumor initiating or complete carcinogenic activity.

  18. Transient receptor potential channel ankyrin-1 is not a cold sensor for autonomic thermoregulation in rodents.

    Science.gov (United States)

    de Oliveira, Cristiane; Garami, Andras; Lehto, Sonya G; Pakai, Eszter; Tekus, Valeria; Pohoczky, Krisztina; Youngblood, Beth D; Wang, Weiya; Kort, Michael E; Kym, Philip R; Pinter, Erika; Gavva, Narender R; Romanovsky, Andrej A

    2014-03-26

    The rodent transient receptor potential ankyrin-1 (TRPA1) channel has been hypothesized to serve as a temperature sensor for thermoregulation in the cold. We tested this hypothesis by using deletion of the Trpa1 gene in mice and pharmacological blockade of the TRPA1 channel in rats. In both Trpa1(-/-) and Trpa1(+/+) mice, severe cold exposure (8°C) resulted in decreases of skin and deep body temperatures to ∼8°C and 13°C, respectively, both temperatures being below the reported 17°C threshold temperature for TRPA1 activation. Under these conditions, Trpa1(-/-) mice had the same dynamics of body temperature as Trpa1(+/+) mice and showed no weakness in the tail skin vasoconstriction response or thermogenic response to cold. In rats, the effects of pharmacological blockade were studied by using two chemically unrelated TRPA1 antagonists: the highly potent and selective compound A967079, which had been characterized earlier, and the relatively new compound 43 ((4R)-1,2,3,4-tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d]pyrimidin-5-one), which we further characterized in the present study and found to be highly potent (IC50 against cold of ∼8 nm) and selective. Intragastric administration of either antagonist at 30 mg/kg before severe (3°C) cold exposure did not affect the thermoregulatory responses (deep body and tail skin temperatures) of rats, even though plasma concentrations of both antagonists well exceeded their IC50 value at the end of the experiment. In the same experimental setup, blocking the melastatin-8 (TRPM8) channel with AMG2850 (30 mg/kg) attenuated cold-defense mechanisms and led to hypothermia. We conclude that TRPA1 channels do not drive autonomic thermoregulatory responses to cold in rodents.

  19. In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis.

    Science.gov (United States)

    Kleinstreuer, Nicole C; Dix, David J; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Paul, Katie B; Reif, David M; Crofton, Kevin M; Hamilton, Kerry; Hunter, Ronald; Shah, Imran; Judson, Richard S

    2013-01-01

    Thousands of untested chemicals in the environment require efficient characterization of carcinogenic potential in humans. A proposed solution is rapid testing of chemicals using in vitro high-throughput screening (HTS) assays for targets in pathways linked to disease processes to build models for priority setting and further testing. We describe a model for predicting rodent carcinogenicity based on HTS data from 292 chemicals tested in 672 assays mapping to 455 genes. All data come from the EPA ToxCast project. The model was trained on a subset of 232 chemicals with in vivo rodent carcinogenicity data in the Toxicity Reference Database (ToxRefDB). Individual HTS assays strongly associated with rodent cancers in ToxRefDB were linked to genes, pathways, and hallmark processes documented to be involved in tumor biology and cancer progression. Rodent liver cancer endpoints were linked to well-documented pathways such as peroxisome proliferator-activated receptor signaling and TP53 and novel targets such as PDE5A and PLAUR. Cancer hallmark genes associated with rodent thyroid tumors were found to be linked to human thyroid tumors and autoimmune thyroid disease. A model was developed in which these genes/pathways function as hypothetical enhancers or promoters of rat thyroid tumors, acting secondary to the key initiating event of thyroid hormone disruption. A simple scoring function was generated to identify chemicals with significant in vitro evidence that was predictive of in vivo carcinogenicity in different rat tissues and organs. This scoring function was applied to an external test set of 33 compounds with carcinogenicity classifications from the EPA's Office of Pesticide Programs and successfully (p = 0.024) differentiated between chemicals classified as "possible"/"probable"/"likely" carcinogens and those designated as "not likely" or with "evidence of noncarcinogenicity." This model represents a chemical carcinogenicity prioritization tool supporting targeted

  20. Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Michael R Due

    Full Text Available Approximately 60% of morphine is glucuronidated to morphine-3-glucuronide (M3G which may aggravate preexisting pain conditions. Accumulating evidence indicates that M3G signaling through neuronal Toll-like receptor 4 (TLR4 may be central to this proalgesic signaling event. These events are known to include elevated neuronal excitability, increased voltage-gated sodium (NaV current, tactile allodynia and decreased opioid analgesic efficacy. Using an in vitro ratiometric-based calcium influx analysis of acutely dissociated small and medium-diameter neurons derived from lumbar dorsal root ganglion (DRG, we observed that M3G-sensitive neurons responded to lipopolysaccharide (LPS and over 35% of these M3G/LPS-responsive cells exhibited sensitivity to capsaicin. In addition, M3G-exposed sensory neurons significantly increased excitatory activity and potentiated NaV current as measured by current and voltage clamp, when compared to baseline level measurements. The M3G-dependent excitability and potentiation of NaV current in these sensory neurons could be reversed by the addition of carbamazepine (CBZ, a known inhibitor of several NaV currents. We then compared the efficacy between CBZ and morphine as independent agents, to the combined treatment of both drugs simultaneously, in the tibial nerve injury (TNI model of neuropathic pain. The potent anti-nociceptive effects of morphine (5 mg/kg, i.p. were observed in TNI rodents at post-injury day (PID 7-14 and absent at PID21-28, while administration of CBZ (10 mg/kg, i.p. alone failed to produce anti-nociceptive effects at any time following TNI (PID 7-28. In contrast to either drug alone at PID28, the combination of morphine and CBZ completely attenuated tactile hyperalgesia in the rodent TNI model. The basis for the potentiation of morphine in combination with CBZ may be due to the effects of a latent upregulation of NaV1.7 in the DRG following TNI. Taken together, our observations demonstrate a

  1. Rodents on pig and chicken farms – a potential threat to human and animal health

    Directory of Open Access Journals (Sweden)

    Annette Backhans

    2012-02-01

    Full Text Available Rodents can cause major problems through spreading various diseases to animals and humans. The two main species of rodents most commonly found on farms around the world are the house mouse (Mus musculus and the brown rat (Rattus norvegicus. Both species are omnivorous and can breed year-round under favourable conditions. This review describes the occurrence of pathogens in rodents on specialist pig and chicken farms, which are usually closed units with a high level of bio-security. However, wild rodents may be difficult to exclude completely, even from these sites, and can pose a risk of introducing and spreading pathogens. This article reviews current knowledge regarding rodents as a hazard for spreading disease on farms. Most literature available regards zoonotic pathogens, while the literature regarding pathogens that cause disease in farm animals is more limited.

  2. Cobalt and antimony: genotoxicity and carcinogenicity.

    Science.gov (United States)

    De Boeck, Marlies; Kirsch-Volders, Micheline; Lison, Dominique

    2003-12-10

    The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with

  3. The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.

    Science.gov (United States)

    Soffritti, Morando; Padovani, Michela; Tibaldi, Eva; Falcioni, Laura; Manservisi, Fabiana; Belpoggi, Fiorella

    2014-04-01

    Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health.

  4. Genotoxicity and carcinogenicity risk of carbon nanotubes.

    Science.gov (United States)

    Toyokuni, Shinya

    2013-12-01

    Novel materials are often commercialized without a complete assessment of the risks they pose to human health because such assessments are costly and time-consuming; additionally, sometimes the methodology needed for such an assessment does not exist. Carbon nanotubes have the potential for widespread application in engineering, materials science and medicine. However, due to the needle-like shape and high durability of multiwalled carbon nanotubes (MWCNTs), concerns have been raised that they may induce asbestos-like pathogenicity when inhaled. Indeed, experiments in rodents supported this hypothesis. Notably, the genetic alterations in MWCNT-induced rat malignant mesothelioma were similar to those induced by asbestos. Single-walled CNTs (SWCNTs) cause mitotic disturbances in cultured cells, but thus far, there has been no report that SWCNTs are carcinogenic. This review summarizes the recent noteworthy publications on the genotoxicity and carcinogenicity of CNTs and explains the possible molecular mechanisms responsible for this carcinogenicity. The nanoscale size and needle-like rigid structure of CNTs appear to be associated with their pathogenicity in mammalian cells, where carbon atoms are major components in the backbone of many biomolecules. Publishing adverse events associated with novel materials is critically important for alerting people exposed to such materials. CNTs still have a bright future with superb economic and medical merits. However, appropriate regulation of the production, distribution and secondary manufacturing processes is required, at least to protect the workers.

  5. Spatial analysis of potential carcinogenic risks associated with ingesting arsenic in aquacultural tilapia (Oreochromis mossambicus) in blackfoot disease hyperendemic areas.

    Science.gov (United States)

    Jang, Cheng-Shin; Liu, Chen-Wuing; Lin, Kao-Hung; Huang, Feng-Mei; Wang, Sheng-Wei

    2006-03-01

    This work analyzed spatially potential carcinogenic risks associated with ingesting arsenic (As) contents in aquacultural tilapia (Oreochromis mossambicus) in coastal regions of southwestern Taiwan, where the blackfoot disease prevails. Sequential indicator simulation (SIS) was used to reproduce As exposure distributions in groundwater based on their three-dimensional variability. A target cancer risk (TR) associated with ingesting As in aquacultural tilapia was calculated to evaluate the potential risk to human health. Owing to sparse measured data, Monte Carlo simulation and SIS properly accounted for the uncertainty of assessed parameters. The probabilistic risk assessment formulated suitable strategies under various remedial stages. Aquacultural regions with high risks were mapped to elucidate the safety of groundwater use at different depths. Many TRs determined from the risks at the 75th and 95th percentiles exceed one millionth in the regions, indicating that ingesting tilapia farmed in the highly As-polluted regions poses potential cancer threats to human health. The 75th percentile of TR is considered in formulating a remedial strategy for the aquacultural use of groundwater in the preliminary stage. Additionally, this study suggests reducing the use of groundwater in aquaculture or changing the depths from which groundwater is withdrawn in the areas with high risks of cancer.

  6. Potential Roles of Pigs, Small Ruminants, Rodents, and Their Flea Vectors in Plague Epidemiology in Sinda District, Eastern Zambia.

    Science.gov (United States)

    Nyirenda, Stanley S; Hang'ombe, Bernard M; Kilonzo, Bukheti S; Kangwa, Henry L; Mulenga, Evans; Moonga, Ladslav

    2017-05-01

    A cross-sectional study was conducted in the Eastern part of Zambia that previously reported a plague outbreak. The aim of the study was to evaluate the potential role of pigs, goats, and sheep as sero-surveillance hosts for monitoring plague, and to investigate the flea vectors and potential reservoir hosts to establish the current status of plague endemicity in the district. Serum samples were collected from 96 rodents, 10 shrews, 245 domestic pigs, 232 goats, and 31 sheep, whereas 106 organs were eviscerated from rodents and shrews. As for fleas, 1,064 Echidnophaga larina Jordan & Rothschild, 7 Xenopsylla cheopis (Rothschild), and 382 Echidnophaga gallinacea (Westwood) were collected from these animals in 34 villages. Enzyme-Linked Immunosorbent Assay (ELISA) and Polymerase Chain Reaction (PCR) tests were performed on serum, and organs and fleas to determine IgG antibodies against Fraction 1 antigen and pla gene of Yersinia pestis, respectively. ELISA results showed that 2.83% (95% CI = 0.59-8.05) rodents, 9.0% (95% CI = 5.71-13.28) domestic pigs, 4.7% (95% CI = 2.39-8.33) goats, and 3.2% (95% CI = 0.08-16.70) sheep were positive for IgG antibodies against Fra1 antigen of Y. pestis. On PCR, 8.4% (95% CI = 3.96-15.51) of the rodents were detected with Y. pestis pla gene, whereas all fleas were found negative. The common fleas identified were E. larina from pigs, whereas X. cheopis were the only fleas collected from rodents. The presence of sero-positive animals as well as the occurrence of X. cheopis on local rodents suggests that Y. pestis remains a risk in the district. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Plant extracts, spices, and essential oils inactivate E. coli O157:H7 pathogens and reduce formation of potentially carcinogenic heterocyclic amines in grilled beef patties

    Science.gov (United States)

    Meats need to be sufficiently heated to inactivate foodborne pathogens such as Escherichia coli O157:H7. High-temperature heat treatment used to prepare well-done meats could, however, increase the formation of potentially carcinogenic heterocyclic amines (HCAs). The objective of this study was to ...

  8. Amelioratory effect of coenzyme Q10 on potential human carcinogen Microcystin-LR induced toxicity in mice.

    Science.gov (United States)

    Lone, Yaqoob; Bhide, Mangla; Koiri, Raj Kumar

    2017-04-01

    Microcystins are a group of cyclic heptapeptide toxins produced by cyanobacteria. More than 100 microcystin analogues have been detected, among which microcystin-LR is the most abundant and toxic variant. Present study was designed to reveal whether potential human carcinogen microcystin-LR could imbalance the glycolytic-oxidative-nitrosative status of heart, kidney and spleen of mice and also to explore the amelioratory effect of coenzyme Q10 on microcystin-LR induced toxicity. Microcystin-LR was administered at a dose of 10 μg/kg bw/day, ip for 14 days in male mice. In microcystin-LR treated mice as compared to control, significant increase in the level of lipid peroxidation, hydrogen peroxide, lactate dehydrogenase, nitric oxide with a concomitant decrease in the level of glutathione was observed, suggesting microcystin-LR induced toxicity via induction of oxidative-nitrosative-glycolytic pathway. Although several studies have evaluated numerous antioxidants but still there is no effective chemoprotectant against microcystin-LR induced toxicity. When microcystin-LR treated mice were co-administered coenzyme Q10 (10 mg/kg bw/day, im) for 14 days, it was observed that coenzyme Q10 ameliorates microcystin-LR induced toxicity via modulation of glycolytic-oxidative-nitrosative stress pathway. Thus, the results suggest that coenzyme Q10 has a potential to be developed as preventive agent against microcystin-LR induced toxicity.

  9. Sleep Deprivation and Caffeine Treatment Potentiate Photic Resetting of the Master Circadian Clock in a Diurnal Rodent.

    Science.gov (United States)

    Jha, Pawan Kumar; Bouâouda, Hanan; Gourmelen, Sylviane; Dumont, Stephanie; Fuchs, Fanny; Goumon, Yannick; Bourgin, Patrice; Kalsbeek, Andries; Challet, Etienne

    2017-04-19

    Circadian rhythms in nocturnal and diurnal mammals are primarily synchronized to local time by the light/dark cycle. However, nonphotic factors, such as behavioral arousal and metabolic cues, can also phase shift the master clock in the suprachiasmatic nuclei (SCNs) and/or reduce the synchronizing effects of light in nocturnal rodents. In diurnal rodents, the role of arousal or insufficient sleep in these functions is still poorly understood. In the present study, diurnal Sudanian grass rats, Arvicanthis ansorgei, were aroused at night by sleep deprivation (gentle handling) or caffeine treatment that both prevented sleep. Phase shifts of locomotor activity were analyzed in grass rats transferred from a light/dark cycle to constant darkness and aroused in early night or late night. Early night, but not late night, sleep deprivation induced a significant phase shift. Caffeine on its own induced no phase shifts. Both sleep deprivation and caffeine treatment potentiated light-induced phase delays and phase advances in response to a 30 min light pulse, respectively. Sleep deprivation in early night, but not late night, potentiated light-induced c-Fos expression in the ventral SCN. Caffeine treatment in midnight triggered c-Fos expression in dorsal SCN. Both sleep deprivation and caffeine treatment potentiated light-induced c-Fos expression in calbindin-containing cells of the ventral SCN in early and late night. These findings indicate that, in contrast to nocturnal rodents, behavioral arousal induced either by sleep deprivation or caffeine during the sleeping period potentiates light resetting of the master circadian clock in diurnal rodents, and activation of calbindin-containing suprachiasmatic cells may be involved in this effect.SIGNIFICANCE STATEMENT Arousing stimuli have the ability to regulate circadian rhythms in mammals. Behavioral arousal in the sleeping period phase shifts the master clock in the suprachiasmatic nuclei and/or slows down the photic

  10. Carcinogenic potential of duodenal reflux juice from patients with long-standing postgastrectomy

    Institute of Scientific and Technical Information of China (English)

    Zhe Fu Ma; Zhong Yu Wang; Jun Ran Zhang; Peng Gong; Hai Long Chen

    2001-01-01

    AIM To determine, whether study on thecarcinogenic potential of reflux juice frompatients with remote gastrectomy could clarifythe inherent relationship between duodenalreflux and gastric stump cancer.METHODS A total of 37 reflux juice samples(13 Billroth T, 24 Billroth Ⅱ ) were employed inthe present study. A two- stage transformationassay using BALB/c 3T3 cells was carried out totest the initiating or promoting activity of thesesamples.RESULTS Two of 18 (11.1%) reflux samplesexerted initiating activities, whereas 9/19(47.4%) samples enhanced the MNNG-initiafingcell transformation, suggesting the duodenalreflux juice might more frequently possess thetumor-promoter activity (P = 0. 029). In addition,there was no difference in initiating activities ofthe samples irrespective of surgical procedures(P=0.488), while Billroth Ⅱ samples exhibitedstronger tumor-promoter activity than Billroth Ⅰsamples (P = 0.027). Furthermore, the promoteractivities were well correlated with thehistological changes of the stomas (rs = 0.625,P = 0.004), but neither their cytotoxicities norinitiating activities had this correlation( Probabilities were 0.523 and 0.085,respectively).CONCLUSION The duodenal reflux juice frompatients with remote postgastrectomy did havecarcinogenic potential, and suggested thattumor-promoting activity should principallyaccount for the high incidence of gastric cancerin gastrectomy patients. In contrast, it isdifficult to explain the high stump-cancerincidence with the "N-nitroso compounds"theory-a popular theory for the intact stomachcarcinogenesis, and it seemed to be justified tofocus chemoprevention of this cancer on thetumor-promoting potential of reflux juice.

  11. Consumption of organic meat does not diminish the carcinogenic potential associated with the intake of persistent organic pollutants (POPs).

    Science.gov (United States)

    Hernández, Ángel Rodríguez; Boada, Luis D; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valerón, Pilar F; Camacho, María; Zumbado, Manuel; Almeida-González, Maira; Henríquez-Hernández, Luis A; Luzardo, Octavio P

    2017-02-01

    Numerous studies have shown an epidemiological link between meat consumption and the incidence of cancer, and it has been suggested that this relationship may be motivated by the presence of carcinogenic contaminants on it. Among the most frequently detected contaminants in meat are several types of persistent organic pollutants (POPs), and it is well known that many of them are carcinogenic. On the other hand, an increasing number of consumers choose to feed on what are perceived as healthier foods. Thus, the number of consumers of organic food is growing. However, environmental contamination by POPs is ubiquitous, and it is therefore unlikely that the practices of organic food production are able to prevent this contamination. To test this hypothesis, we acquired 76 samples of meat (beef, chicken, and lamb) of two modes of production (organic and conventional) and quantified their levels of 33 carcinogenic POPs. On this basis, we determined the human meat-related daily dietary exposure to these carcinogens using as a model a population with a high consumption of meat, such as the Spanish population. The maximum allowable meat consumption for this population and the carcinogenic risk quotients associated with the current pattern of consumption were calculated. As expected, no sample was completely free of carcinogenic contaminants, and the differences between organically and conventionally produced meats were minimal. According to these results, the current pattern of meat consumption exceeded the maximum limits, which are set according to the levels of contaminations, and this is associated with a relevant carcinogenic risk. Strikingly, the consumption of organically produced meat does not diminish this carcinogenic risk, but on the contrary, it seems to be even higher, especially that associated with lamb consumption.

  12. Radio frequency radiation (RFR): the nature of exposure and carcinogenic potential.

    Science.gov (United States)

    Valberg, P A

    1997-05-01

    Epidemiologic evidence on the relation between radio-frequency radiation (RFR) and cancer is reviewed. Radio-wave communications are used extensively in modern society; thus, we are all subject to RFR created by radio, television, wireless telephony, emergency communications, radar, etc. Interest in the health effects of RFR has been motivated by the rapid growth in wireless communications and by media reports expressing concern that specific diseases may be caused by RFR exposure, e.g., from cellular telephone handsets. Due to the ubiquitous presence of RFR, the public health implication of any connection between RFR and cancer risk is potentially significant. (It is important to keep RFR distinct from power-line electromagnetic fields.) Comparison of potential risks from RFR exposure with other occupational and environmental health risks requires evaluating the level of support from available epidemiology, from studies with laboratory animals, and from mechanistic or biophysical information about the interaction of RFR with living tissues. A large number of studies have been done with laboratory animals and with in vitro systems; a more limited set of epidemiologic studies is available. Effects from RFR exposure that lead to temperature increases have been consistently reported, but 'non-thermal' effects have not been substantiated. Also, there are no mechanistic theories that support 'non-thermal' interactions with biology. Evidence to support a causal relationship between exposure to RFR and human cancers is scant. Our present state of knowledge about exposure, mechanisms, epidemiology, and animal studies does not identify significant cancer risks.

  13. Potential mechanism for pentachlorophenol-induced carcinogenicity: a novel mechanism for metal-independent production of hydroxyl radicals.

    Science.gov (United States)

    Zhu, Ben-Zhan; Shan, Guo-Qiang

    2009-06-01

    ,4-benzoquinone (TrCBQ-OOH) intermediate, which decomposes homolytically to produce (*)OH. These findings represent a novel mechanism of (*)OH formation not requiring the involvement of redox-active transition metal ions and may partly explain the potential carcinogenicity of the widely used biocides such as PCP and other polyhalogenated aromatic compounds.

  14. Mutagenic and carcinogenic potential of a textile azo dye processing plant effluent that impacts a drinking water source.

    Science.gov (United States)

    Alves de Lima, Rodrigo Otávio; Bazo, Ana Paula; Salvadori, Daisy Maria Fávero; Rech, Célia Maria; de Palma Oliveira, Danielle; de Aragão Umbuzeiro, Gisela

    2007-01-10

    river, Chemosphere 60 (2005) 55-64]. Therefore, it is important to evaluate the possible risks involved in the human consumption of this contaminated water. With that objective, one sample of the cited industrial effluent was tested for carcinogenicity in the aberrant crypt foci medium-term assay in colon of Wistar rats. The rats received the effluent in natura through drinking water at concentrations of 0.1%, 1%, and 10%. The effluent mutagenicity was also confirmed in the Salmonella/microsome assay with the strains TA98 and YG1041. There was an increased number of preneoplastic lesions in the colon of rats exposed to concentrations of 1% and 10% of the effluent, and a positive response for both Salmonella strains tested. These results indicate that the discharge of the effluent should be avoided in waters used for human consumption and show the sensitivity of the ACF crypt foci assay as an important tool to evaluate the carcinogenic potential of environmental complex mixtures.

  15. Possible carcinogenic potential of dimethyl dimethoxy biphenyl dicarboxylate in experimental animals

    Directory of Open Access Journals (Sweden)

    Sanaa Sabet Botros

    2016-01-01

    Full Text Available Dimethyl dimethoxy biphenyl dicarboxylate (DDB has been extensively used in the treatment of liver diseases accounting for 1-6% of the global disease burden. Cell replication, DNA synthesis, and proliferation, providing significant information about behavior of cells were examined in mice exposed to subchronic administration with DDB. Conventional liver functions specifically gamma-glutamyltransferase (γ-GT, a marker expressing liver canceration was also investigated. Normal mice were allocated into two groups each of 10 mice. The 1 st and 2 nd groups were treated with DDB in a dose of 50 mg/kg/day, 5 days/week for 1 month and 3 months, respectively. Comparable groups of normal mice were left without treatment as controls. Compared to normal control group, animals receiving DDB for 3 months showed marked elevations of both alanine aminotransferase and γ-GT, significant inhibition in cytochrome P450, a significant increase in the mean ploidy and 4C with moderate to marked increase in S-phase populations and the number of proliferating cell nuclear antigen-positive cells. In conclusion, this is the first report on the potential relationship between the subchronic administration of DDB and the increase in the hepatocyte proliferation, cell replication and DNA synthesis that may raise an alarm regarding possible DDB insult on the biological behavior of cells.

  16. Quantitative comparison between in vivo DNA adduct formation from exposure to selected DNA-reactive carcinogens, natural background levels of DNA adduct formation and tumour incidende in rodent bioassays

    NARCIS (Netherlands)

    Paini, A.; Scholz, G.; Marin-Kuan, M.; Schilter, B.; O'Brien, J.; Bladeren, van P.J.; Rietjens, I.

    2011-01-01

    This study aimed at quantitatively comparing the occurrence/formation of DNA adducts with the carcinogenicity induced by a selection of DNA-reactive genotoxic carcinogens. Contrary to previous efforts, we used a very uniform set of data, limited to in vivo rat liver studies in order to investigate w

  17. Quantitative comparison between in vivo DNA adduct formation from exposure to selected DNA-reactive carcinogens, natural background levels of DNA adduct formation and tumour incidende in rodent bioassays

    NARCIS (Netherlands)

    Paini, A.; Scholz, G.; Marin-Kuan, M.; Schilter, B.; O'Brien, J.; Bladeren, van P.J.; Rietjens, I.

    2011-01-01

    This study aimed at quantitatively comparing the occurrence/formation of DNA adducts with the carcinogenicity induced by a selection of DNA-reactive genotoxic carcinogens. Contrary to previous efforts, we used a very uniform set of data, limited to in vivo rat liver studies in order to investigate

  18. Assessment of genotoxic potential of Cr(VI) in the mouse duodenum: an in silico comparison with mutagenic and nonmutagenic carcinogens across tissues.

    Science.gov (United States)

    Thompson, Chad M; Gregory Hixon, J; Proctor, Deborah M; Haws, Laurie C; Suh, Mina; Urban, Jonathan D; Harris, Mark A

    2012-10-01

    In vitro studies on hexavalent chromium [Cr(VI)] indicate that reduced forms of this metal can interact with DNA and cause mutations. Recently, Cr(VI) was shown to induce intestinal tumors in mice; however, Cr(VI) elicited redox changes, cytotoxicity and hyperplasia - suggesting involvement of tissue injury rather than direct mutagenesis. Moreover, toxicogenomic analyses indicated limited evidence for DNA damage responses. Herein, we extend these toxicogenomic analyses by comparing the gene expression patterns elicited by Cr(VI) with those of four mutagenic and four nonmutagenic carcinogens. To date, toxicogenomic profiles for mutagenic and nonmutagenic duodenal carcinogens do not exist, thus duodenal gene changes in mice were compared to those elicited by hepatocarcinogens. Specifically, duodenal gene changes in mice following exposure to Cr(VI) in drinking water were compared to hepatic gene changes previously identified as potentially discriminating mutagenic and nonmutagenic hepatocarcinogens. Using multivariate statistical analyses (including logistic regression classification), the Cr(VI) gene responses clustered apart from mutagenic carcinogens and closely with nonmutagenic carcinogens. These findings are consistent with other intestinal data supporting a nonmutagenic mode of action (MOA). These findings may be useful as part of a full weight of evidence MOA evaluation for Cr(VI)-induced intestinal carcinogenesis. Limitations to this analysis will also be discussed.

  19. Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine.

    Science.gov (United States)

    Fukumoto, Kenichi; Toki, Hidetoh; Iijima, Michihiko; Hashihayata, Takashi; Yamaguchi, Jun-Ichi; Hashimoto, Kenji; Chaki, Shigeyuki

    2017-04-01

    The rapid-acting and long-lasting antidepressant effects of (R,S)-ketamine have recently gained much attention. Although (S)-ketamine has been studied as an active isomer, recent evidence suggests that (R)-ketamine exhibits longer-lasting antidepressant effects than (S)-ketamine in rodents. However, the antidepressant potential of (R)-ketamine has not been fully addressed. In the present study, we compared the antidepressant effects of (R)-ketamine with those of (S)-ketamine in animal models of depression, including a model that is refractory to current medications. Both (R)-ketamine and (S)-ketamine exhibited antidepressant effects at 30 minutes as well as at 24 hours after administration in forced-swimming and tail-suspension tests in mice. At 48 hours after administration, however, (R)-ketamine still exerted a significant antidepressant effect in the tail-suspension test, whereas the effect of (S)-ketamine was no longer observed. Moreover, (R)-ketamine, but not (S)-ketamine, significantly reversed the depressive-like behavior induced by repeated treatments with corticosterone in rats at 24 hours after a single administration. This effect was attenuated by an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, suggesting the involvement of AMPA receptor stimulation in the effects. Both (R)-ketamine and (S)-ketamine exhibited practically the same exposure levels in plasma, brain, and cerebrospinal fluid in mice and rats, and both compounds were rapidly eliminated from plasma (S)-ketamine in animal models of depression. Moreover, our study is the first to demonstrate that (R)-ketamine exerted a sustained antidepressant effect even in a model that is refractory to currently prescribed antidepressants.

  20. Nicotinic modulation of auditory evoked potential electroencephalography in a rodent neurodevelopmental model of schizophrenia.

    Science.gov (United States)

    Kohlhaas, Kathy L; Robb, Holly M; Roderwald, Victoria A; Rueter, Lynne E

    2015-10-15

    Schizophrenia is a chronic disease that has been hypothesized to be linked to neurodevelopmental abnormalities. Schizophrenia patients exhibit impairments in basic sensory processing including sensory gating deficits in P50 and mismatch negativity (MMN). Neuronal nicotinic acetylcholine receptor (nAChR) agonists have been reported to attenuate these deficits. Gestational exposure of rats to methylazoxymethanol acetate (MAM) at embryonic day 17 leads to developmental disruption of the limbic-cortical system. MAM exposed offspring show neuropathological and behavioral changes that have similarities with those seen in schizophrenia. In this study, we aimed to assess whether N40 auditory sensory gating (the rodent form of P50 gating) and MMN deficits as measures of auditory evoked potential (AEP) electroencephalography (EEG) are present in MAM rats and whether nAChR agonists could attend the deficit. E17 male MAM and sham rats were implanted with cortical electrodes at 2 months of age. EEG recordings evaluating N40 gating and MMN paradigms were done comparing effects of vehicle (saline), nicotine and the α7 agonist ABT-107. Deficits were seen for MAM rats compared to sham animals in both N40 auditory sensory gating and MMN AEP recordings. There was a strong trend for N40 deficits to be attenuated by both nicotine (0.16mg/kg i.p. base) and ABT-107 (1.0mg/kg i.p. base). MMN deficits were significantly attenuated by ABT-107 but not by nicotine. These data support the MAM model as a useful tool for translating pharmacodynamic effects in clinical medicine studies of novel therapeutic treatments for schizophrenia.

  1. Modeling impacts of climate change on the potential distribution of the carcinogenic liver fluke, Opisthorchis viverrini, in Thailand.

    Science.gov (United States)

    Suwannatrai, A; Pratumchart, K; Suwannatrai, K; Thinkhamrop, K; Chaiyos, J; Kim, C S; Suwanweerakamtorn, R; Boonmars, T; Wongsaroj, T; Sripa, B

    2017-01-01

    Global climate change is now regarded as imposing a significant threat of enhancing transmission of parasitic diseases. Maximum entropy species distribution modeling (MaxEnt) was used to explore how projected climate change could affect the potential distribution of the carcinogenic liver fluke, Opisthorchis viverrini, in Thailand. A range of climate variables was used: the Hadley Global Environment Model 2-Earth System (HadGEM2-ES) climate change model and also the IPCC scenarios A2a for 2050 and 2070. Occurrence data from surveys conducted in 2009 and 2014 were obtained from the Department of Disease Control, Ministry of Public Health, Thailand. The MaxEnt model performed better than random for O. viverrini with training AUC values greater than 0.8 under current and future climatic conditions. The current distribution of O. viverrini is significantly affected by precipitation and minimum temperature. According to current conditions, parts of Thailand climatically suitable for O. viverrini are mostly in the northeast and north, but the parasite is largely absent from southern Thailand. Under future climate change scenarios, the distribution of O. viverrini in 2050 should be significantly affected by precipitation, maximum temperature, and mean temperature of the wettest quarter, whereas in 2070, significant factors are likely to be precipitation during the coldest quarter, maximum, and minimum temperatures. Maps of predicted future distribution revealed a drastic decrease in presence of O. viverrini in the northeast region. The information gained from this study should be a useful reference for implementing long-term prevention and control strategies for O. viverrini in Thailand.

  2. Mechanisms of the different DNA adduct forming potentials of the urban air pollutants 2-nitrobenzanthrone and carcinogenic 3-nitrobenzanthrone.

    Science.gov (United States)

    Stiborová, Marie; Martínek, Václav; Svobodová, Martina; Sístková, Jana; Dvorák, Zdenek; Ulrichová, Jitka; Simánek, Vilím; Frei, Eva; Schmeiser, Heinz H; Phillips, David H; Arlt, Volker M

    2010-07-19

    2-Nitrobenzanthrone (2-NBA) has recently been detected in ambient air particulate matter. Its isomer 3-nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust. We compared the efficiencies of human enzymatic systems [hepatic microsomes and cytosols, NAD(P)H:quinone oxidoreductase 1 (NQO1), xanthine oxidase, NADPH:cytochrome P450 reductase, N,O-acetyltransferases, and sulfotransferases] and human primary hepatocytes to activate 2-NBA and its isomer 3-NBA to species forming DNA adducts. In contrast to 3-NBA, 2-NBA was not metabolized at detectable levels by the tested human enzymatic systems and enzymes expressed in human hepatocytes, and no DNA adducts detectable by (32)P-postlabeling were generated by 2-NBA. Even NQO1, the most efficient human enzyme to bioactive 3-NBA, did not activate 2-NBA. Molecular docking of 2-NBA and 3-NBA to the active site of NQO1 showed similar binding affinities; however, the binding orientation of 2-NBA does not favor the reduction of the nitro group. This was in line with the inhibition of 3-NBA-DNA adduct formation by 2-NBA, indicating that 2-NBA can compete with 3-NBA for binding to NQO1, thereby decreasing the metabolic activation of 3-NBA. In addition, the predicted equilibrium conditions favor a 3 orders of magnitude higher dissociation of N-OH-3-ABA in comparison to N-OH-2-ABA. These findings explain the very different genotoxicity, mutagenicity, and DNA adduct forming potential of the two compounds. Collectively, our results suggest that 2-NBA possesses a relatively lower risk to humans than 3-NBA.

  3. Toxoplasmosis seroprevalence in wild small rodents, potentially preys of ocelots in north-eastern Mexico

    Directory of Open Access Journals (Sweden)

    Rendón-Franco Emilio

    2014-01-01

    Full Text Available The aim of this study was to assess the prevalence of Toxoplasma gondii infection in rodents that coexist with ocelots in north-eastern Mexico. Eighty rodents of five genera were captured and their serum samples tested for specific IgG antibodies to T. gondii by in-house indirect ELISA using three different conjugates. Prevalences of 7% (3/44 and 33% (4/12 were found in Sigmodon hispidus and Liomys irroratus, respectively, and were significantly different. All Baiomys taylori and Oligoryzomys fulvescens were negative for the presence of anti-T. gondii IgG antibodies. The samples from Peromyscus spp. could not be analyzed because none of the three conjugates tested recognized their immunoglobulins. Infection was confirmed in one single specimen of L. irroratus by qPCR, which generated an estimate of 146 parasites per mg of muscle tissue. The results strongly support the notion of active T. gondii transmission between rodents and felines in this zone of Mexico and an important role of some rodent species in the sylvatic cycle of T. gondii.

  4. Corticostriatal field potentials are modulated at delta and theta frequencies during interval-timing task in rodents

    Directory of Open Access Journals (Sweden)

    Eric B Emmons

    2016-04-01

    Full Text Available Organizing movements in time is a critical and highly conserved feature of mammalian behavior. Temporal control of action requires corticostriatal networks. We investigate these networks in rodents using a two-interval timing task while recording local field potentials in medial frontal cortex or dorsomedial striatum. Consistent with prior work, we found cue-triggered delta (1-4 Hz and theta activity (4-8 Hz primarily in rodent medial frontal cortex. We observed delta activity across temporal intervals in medial frontal cortex and dorsomedial striatum. Rewarded responses were associated with increased delta activity in medial frontal cortex. Activity in theta bands in medial frontal cortex and delta bands in the striatum was linked with the timing of responses. These data suggest both delta and theta activity in frontostriatal networks are modulated during interval timing and that activity in these bands may be involved in the temporal control of action.

  5. Carcinogenicity/tumour promotion by NDL PCB

    Energy Technology Data Exchange (ETDEWEB)

    Schrenk, D. [Kaiserslautern Univ. (Germany). Food Chemistry and Environmental Toxicology

    2004-09-15

    Polychlorinated biphenyls (PCBs) belong to the group of persistent environmental pollutants exhibiting neurotoxic, teratogenic and tumour-promoting effects in experimental animal models. PCB congeners can be divided into 'dioxinlike' and 'non-dioxinlike' congeners on the basis of their ability to act as aryl hydrocarbon receptor (AhR) agonists. Like the most toxic dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 'dioxinlike' PCBs bind to the AhR and show characteristic effects on the expression of AhR-regulated genes including the induction of cytochrome P450 (CYP) 1A1. On the other hand, 'non-dioxinlike' PCB congeners have a lower or no binding affinity to the AhR, but exhibit a 'phenobarbital-type' induction of CYP 2B1/2 activity. A carcinogenic potential of PCBs has been demonstrated with technical mixtures such as Aroclors or Clophens. In these studies the liver and the thyroid gland were found to be the principal target organs of PCB-mediated carcinogenesis in rodents. No studies have been published, however, on the carcinogenicity of individual congeners. In two-stage initiation-promotion protocols in rats, both technical mixtures and individual 'dioxinlike' and 'non-dioxinlike' congeners were reported to act as liver tumour promoters.

  6. Breast cancer in intraductal carcinogen-treated non-human primates.

    Science.gov (United States)

    Lillie, Madeline A; Ambrus, Clara M; Pickren, John W; Akhter, Selina; Islam, Abul; Ambrus, Julian L

    2004-01-01

    Eight female Macaca arctoides monkeys were given dimethylbenzanthracene (DMBA) directly into the milk ducts. During a 4-year observation period, ending with euthanasia and autopsy, no mammary cancers were noticed. However, one animal developed a superficial localized squamous cell carcinoma. DMBA is highly carcinogenic in rodents, e.g. producing a high incidence of breast cancer in C3H mice. It was concluded that carcinogenicity testing should be extended beyond testing in rodents to non-human primates in order to distinguish "primary rodent carcinogens" from those highly active in primates as well. Studies are in progress to study carcinogens in human cell lines transplanted into nu/nu mice.

  7. Carcinogen testing. Fact and fallacy.

    Science.gov (United States)

    Moore, J A

    1988-10-15

    In the absence of human information on the carcinogenicity of chemical substances, one must rely primarily on information from long-term animal testing. Although far from perfect, animal studies seem to be reasonable predictors of the human experience, both qualitatively and quantitatively. Short-term tests for genotoxicity may be helpful for establishing priorities for chemical testing, but they are not as strong indicators of potential carcinogenicity as had been previously thought. New directions in toxicologic research hold the promise for scientists being able to perform more reasoned assessments of carcinogenic risk.

  8. Middle Cerebral Artery Occlusion Model in Rodents: Methods and Potential Pitfalls

    Directory of Open Access Journals (Sweden)

    Fudong Liu

    2011-01-01

    Full Text Available A variety of animal models have been developed for modeling ischemic stroke. The middle cerebral artery occlusion (MCAO model has been utilized extensively, especially in rodents. While the MCAO model provides stroke researchers with an excellent platform to investigate the disease, controversial or even paradoxical results are occasionally seen in the literature utilizing this model. Various factors exert important effects on the outcome in this stroke model, including the age and sex of the animal examined. This paper discusses emerging information on the effects of age and sex on ischemic outcomes after MCAO, with an emphasis on mouse models of stroke.

  9. Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Glass, L.R.; Jones, T.D.; Easterly, C.E.; Walsh, P.J.

    1990-10-01

    It has been hypothesized that results from short-term bioassays will ultimately provide information that will be useful for human health hazard assessment. Historically, the validity of the short-term tests has been assessed using the framework of the epidemiologic/medical screens. In this context, the results of the carcinogen (long-term) bioassay is generally used as the standard. However, this approach is widely recognized as being biased and, because it employs qualitative data, cannot be used to assist in isolating those compounds which may represent a more significant toxicologic hazard than others. In contrast, the goal of this research is to address the problem of evaluating the utility of the short-term tests for hazard assessment using an alternative method of investigation. Chemicals were selected mostly from the list of carcinogens published by the International Agency for Research on Carcinogens (IARC); a few other chemicals commonly recognized as hazardous were included. Tumorigenicity and mutagenicity data on 52 chemicals were obtained from the Registry of Toxic Effects of Chemical Substances (RTECS) and were analyzed using a relative potency approach. The data were evaluated in a format which allowed for a comparison of the ranking of the mutagenic relative potencies of the compounds (as estimated using short-term data) vs. the ranking of the tumorigenic relative potencies (as estimated from the chronic bioassays). Although this was a preliminary investigation, it offers evidence that the short-term tests systems may be of utility in ranking the hazards represented by chemicals which may contribute to increased carcinogenesis in humans as a result of occupational or environmental exposures. 177 refs., 8 tabs.

  10. Carcinogenicity and co-carcinogenicity studies on propoxur in mouse skin.

    Science.gov (United States)

    Shukla, Y; Baqar, S M; Mehrotra, N K

    1998-12-01

    Propoxur (2-isopropoxyphenyl methylcarbamate) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Propoxur exposure is reported to inhibit cholinesterase activity in rodents. Apart from other toxic effects, propoxur was found to possess tumorigenic activity in rats after oral administration. Propoxur does not produce tumours in mice or hamsters, or bladder hyperplasia in dogs and monkeys following oral feeding. In this set of investigations the complete carcinogenic, tumour initiating and promoting potential of propoxur was evaluated in male and female Swiss albino mice, since no information was available following dermal exposure of propoxur. The animals were exposed to propoxur through topical painting on the interscapular region at a dose of 100 mg/kg body weight. The results revealed that propoxur has tumour promoting potential on mouse skin following a two-stage initiation-promotion protocol, but it failed to induce the tumour(s) at a significant level, when tested for tumour initiating and complete carcinogenic property.

  11. Effects of a human milk oligosaccharide, 2'-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents.

    Science.gov (United States)

    Vázquez, Enrique; Barranco, Alejandro; Ramírez, Maria; Gruart, Agnes; Delgado-García, José M; Martínez-Lara, Esther; Blanco, Santos; Martín, María Jesús; Castanys, Esther; Buck, Rachael; Prieto, Pedro; Rueda, Ricardo

    2015-05-01

    Human milk oligosaccharides (HMOs) are unique with regard to their diversity, quantity and complexity, particularly in comparison to bovine milk oligosaccharides. HMOs are associated with functional development during early life, mainly related to immunity and intestinal health. Whether HMOs elicit a positive effect on cognitive capabilities of lactating infants remains an open question. This study evaluated the role of the most abundant HMO, 2'-fucosyllactose (2'-FL), in synaptic plasticity and learning capabilities in rodents. Mice and rats were prepared for the chronic recording of field excitatory postsynaptic potentials evoked at the hippocampal CA3-CA1 synapse. Following chronic oral administration of 2'-FL, both species showed improvements in input/output curves and in long-term potentiation (LTP) evoked experimentally in alert behaving animals. This effect on LTP was related to better performance of animals in various types of learning behavioral tests. Mice were tested for spatial learning, working memory and operant conditioning using the IntelliCage system, while rats were submitted to a fixed-ratio schedule in the Skinner box. In both cases, 2'-FL-treated animals performed significantly better than controls. In addition, chronic administration of 2'-FL increased the expression of different molecules involved in the storage of newly acquired memories, such as the postsynaptic density protein 95, phosphorylated calcium/calmodulin-dependent kinase II and brain-derived neurotrophic factor in cortical and subcortical structures. Taken together, the data show that dietary 2'-FL affects cognitive domains and improves learning and memory in rodents.

  12. Determination of genetic toxicity and potential carcinogenicity in vitro--challenges post the Seventh Amendment to the European Cosmetics Directive.

    Science.gov (United States)

    Tweats, D J; Scott, A D; Westmoreland, C; Carmichael, P L

    2007-01-01

    Genetic toxicology and its role in the detection of carcinogens is currently undergoing a period of reappraisal. There is an increasing interest in developing alternatives to animal testing and the three R's of reduction, refinement and replacement are the basis for EU and national animal protection laws the Seventh Amendment to the EU Cosmetics Directive will ban the marketing of cosmetic/personal care products that contain ingredients that have been tested in animal models. Thus in vivo tests such as the bone marrow micronucleus test, which has a key role in current testing strategies for genotoxicity, will not be available for this class of products. The attrition rate for new, valuable and safe chemicals tested in an in vitro-only testing battery, using the in vitro tests currently established for genotoxicity screening, will greatly increase once this legislation is in place. In addition there has been an explosion of knowledge concerning the cellular and molecular events leading to carcinogenesis. This knowledge has not yet been fully factored into screening chemicals for properties that are not directly linked to mutation induction. Thus there is a pressing need for new, more accurate approaches to determine genotoxicity and carcinogenicity. However, a considerable challenge is presented for these new approaches to be universally accepted and new tests sufficiently validated by March 2009 when the animal testing and marketing bans associated with the Seventh Amendment are due to come into force. This commentary brings together ideas and approaches from several international workshops and meetings to consider these issues.

  13. Biochemical and molecular evidences for the antitumor potential of Ginkgo biloba leaves extract in rodents.

    Science.gov (United States)

    Ahmed, Hanaa H; Shousha, Wafaa Gh; El-Mezayen, Hatem A; El-Toumy, Sayed A; Sayed, Alaa H; Ramadan, Aesha R

    2016-10-14

    Hepatocellular carcinoma (HCC) is one of the deadliest primary cancers, with a 5-year survival rate of 10% or less. This study was undertaken to elucidate the underlying biochemical and molecular mechanisms in favor of N-nitrosodiethylamine-induced hepatocellular carcinoma. Furthermore, the aim of this work was extended to explore the efficacy of Ginkgo biloba leaves extract in deterioration of HCC in rats. In the current study, HCC group experienced significant downregulation of ING-3 gene expression and upregulation of Foxp-1 gene expression in liver. Treatment of HCC groups with Ginkgo biloba leaves extract resulted in upregulation of ING-3 and downregulation of Foxp-1 gene expression in liver. In addition, there was significant increase in serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and glypican-3 (GPC-3) levels in HCC group versus the negative control group. In contrast, the groups with HCC subjected to either high or low dose of Ginkgo biloba leaves extract elicited significant reduction (P Ginkgo biloba leaves extract elicited marked improvement in the histological feature of liver tissue in HCC groups. In conclusion, this research indicated that the carcinogenic potency of N-nitrosodiethylamine targeted multiple systems on the cellular and molecular levels. In addition, the results of the current study shed light on the promising anticancer activity of Ginkgo biloba leaves extract in treatment of hepatocellular carcinoma induced chemically in the experimental model through its apoptotic and antiproliferative properties.

  14. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

    Science.gov (United States)

    Goodson, William H.; Lowe, Leroy; Carpenter, David O.; Gilbertson, Michael; Manaf Ali, Abdul; Lopez de Cerain Salsamendi, Adela; Lasfar, Ahmed; Carnero, Amancio; Azqueta, Amaya; Amedei, Amedeo; Charles, Amelia K.; Collins, Andrew R.; Ward, Andrew; Salzberg, Anna C.; Colacci, Anna Maria; Olsen, Ann-Karin; Berg, Arthur; Barclay, Barry J.; Zhou, Binhua P.; Blanco-Aparicio, Carmen; Baglole, Carolyn J.; Dong, Chenfang; Mondello, Chiara; Hsu, Chia-Wen; Naus, Christian C.; Yedjou, Clement; Curran, Colleen S.; Laird, Dale W.; Koch, Daniel C.; Carlin, Danielle J.; Felsher, Dean W.; Roy, Debasish; Brown, Dustin G.; Ratovitski, Edward; Ryan, Elizabeth P.; Corsini, Emanuela; Rojas, Emilio; Moon, Eun-Yi; Laconi, Ezio; Marongiu, Fabio; Al-Mulla, Fahd; Chiaradonna, Ferdinando; Darroudi, Firouz; Martin, Francis L.; Van Schooten, Frederik J.; Goldberg, Gary S.; Wagemaker, Gerard; Nangami, Gladys N.; Calaf, Gloria M.; Williams, Graeme P.; Wolf, Gregory T.; Koppen, Gudrun; Brunborg, Gunnar; Lyerly, H. Kim; Krishnan, Harini; Ab Hamid, Hasiah; Yasaei, Hemad; Sone, Hideko; Kondoh, Hiroshi; Salem, Hosni K.; Hsu, Hsue-Yin; Park, Hyun Ho; Koturbash, Igor; Miousse, Isabelle R.; Scovassi, A.Ivana; Klaunig, James E.; Vondráček, Jan; Raju, Jayadev; Roman, Jesse; Wise, John Pierce; Whitfield, Jonathan R.; Woodrick, Jordan; Christopher, Joseph A.; Ochieng, Josiah; Martinez-Leal, Juan Fernando; Weisz, Judith; Kravchenko, Julia; Sun, Jun; Prudhomme, Kalan R.; Narayanan, Kannan Badri; Cohen-Solal, Karine A.; Moorwood, Kim; Gonzalez, Laetitia; Soucek, Laura; Jian, Le; D’Abronzo, Leandro S.; Lin, Liang-Tzung; Li, Lin; Gulliver, Linda; McCawley, Lisa J.; Memeo, Lorenzo; Vermeulen, Louis; Leyns, Luc; Zhang, Luoping; Valverde, Mahara; Khatami, Mahin; Romano, Maria Fiammetta; Chapellier, Marion; Williams, Marc A.; Wade, Mark; Manjili, Masoud H.; Lleonart, Matilde E.; Xia, Menghang; Gonzalez Guzman, Michael J.; Karamouzis, Michalis V.; Kirsch-Volders, Micheline; Vaccari, Monica; Kuemmerle, Nancy B.; Singh, Neetu; Cruickshanks, Nichola; Kleinstreuer, Nicole; van Larebeke, Nik; Ahmed, Nuzhat; Ogunkua, Olugbemiga; Krishnakumar, P.K.; Vadgama, Pankaj; Marignani, Paola A.; Ghosh, Paramita M.; Ostrosky-Wegman, Patricia; Thompson, Patricia A.; Dent, Paul; Heneberg, Petr; Darbre, Philippa; Leung, Po Sing; Nangia-Makker, Pratima; Cheng, Qiang (Shawn); Robey, R.Brooks; Al-Temaimi, Rabeah; Roy, Rabindra; Andrade-Vieira, Rafaela; Sinha, Ranjeet K.; Mehta, Rekha; Vento, Renza; Di Fiore, Riccardo; Ponce-Cusi, Richard; Dornetshuber-Fleiss, Rita; Nahta, Rita; Castellino, Robert C.; Palorini, Roberta; Hamid, Roslida A.; Langie, Sabine A.S.; Eltom, Sakina E.; Brooks, Samira A.; Ryeom, Sandra; Wise, Sandra S.; Bay, Sarah N.; Harris, Shelley A.; Papagerakis, Silvana; Romano, Simona; Pavanello, Sofia; Eriksson, Staffan; Forte, Stefano; Casey, Stephanie C.; Luanpitpong, Sudjit; Lee, Tae-Jin; Otsuki, Takemi; Chen, Tao; Massfelder, Thierry; Sanderson, Thomas; Guarnieri, Tiziana; Hultman, Tove; Dormoy, Valérian; Odero-Marah, Valerie; Sabbisetti, Venkata; Maguer-Satta, Veronique; Rathmell, W.Kimryn; Engström, Wilhelm; Decker, William K.; Bisson, William H.; Rojanasakul, Yon; Luqmani, Yunus; Chen, Zhenbang; Hu, Zhiwei

    2015-01-01

    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. PMID:26106142

  15. Potentially zoonotic helminthiases of murid rodents from the Indo-Chinese peninsula: impact of habitat and the risk of human infection.

    Science.gov (United States)

    Chaisiri, Kittipong; Siribat, Praphaiphat; Ribas, Alexis; Morand, Serge

    2015-01-01

    In this study, we report the potential rodent-borne zoonotic helminths in wild-caught murid rodents from four categorized habitats-forest, nonflooded land, irrigated land, and human settlement in seven localities of Thailand, Cambodia, and Lao PDR. Out of 2478 rodent samples, 735 (29.7%) were infected by at least one of the following zoonotic helminth species: Echinostoma malayanum, Echinostoma ilocanum, Plagiorchis muris, Raillietina spp., Hymenolepis diminuta, Hymenolepis nana, Cyclodontostomum purivisi, and Moniliformis moniliformis. Raillietina spp. showed the highest prevalence (13.8%), followed by H. diminuta (8.6%), H. nana (6.7%), and C. purvisi (1.0%). Habitat affected the intensity of helminth infection in murid rodent hosts. Specific habitats favoring each zoonotic helminth species are discussed in relation to the risk of human infection. Season and host maturity influenced intensity of total zoonotic helminths, but there was no influence of host gender. However, in terms of individual helminth species, female rodents were more infected by E. malayanum, E. ilocanum, and C. purvisi than males. Among the rodent species, Rattus tanezumi seems to play the most important role as a reservoir by hosting seven zoonotic heminth species. This rat is ubiquitously found in all types of the habitats, suggesting that it can act as an important bridge species, carrying parasites across different habitats.

  16. Description of Anopheles gabonensis, a new species potentially involved in rodent malaria transmission in Gabon, Central Africa.

    Science.gov (United States)

    Rahola, Nil; Makanga, Boris; Yangari, Patrick; Jiolle, Davy; Fontenille, Didier; Renaud, François; Ollomo, Benjamin; Ayala, Diego; Prugnolle, Franck; Paupy, Christophe

    2014-12-01

    The genus Anopheles includes mosquito vectors of human malaria and arboviruses. In sub-Saharan Africa, the anopheline fauna is rich of nearly 150 species, few of which are anthropophilic and capable of transmitting pathogens to humans. Some of the remaining species are found in forests far from human environments and are vectors of wildlife pathogens. The diversity and the biology of these species have yet to be fully described. As a contribution to furthering knowledge of sylvan Anophelinae, using morphological and molecular tools we describe a new Anopheles species collected in Gabon (Central Africa), which we have named Anopheles gabonensis n. sp. We also molecularly screened this species to detect infections by Plasmodium parasites. The results showed the species to have been infected by Plasmodium vinckei, a rodent parasite. We discuss the role of An. gabonensis n. sp. in the transmission of P. vinckei in the rainforest areas of Central Africa and its potential to transfer pathogens to humans.

  17. Assessment of the carcinogenic potential of high intense-sweeteners through the test for detection of epithelial tumor clones (warts) in Drosophila melanogaster.

    Science.gov (United States)

    Vasconcelos, Mirley Alves; Orsolin, Priscila Capelari; Silva-Oliveira, Rosiane Gomes; Nepomuceno, Júlio César; Spanó, Mário Antônio

    2017-03-01

    High intensity-sweeteners (HIS) are natural or synthetic substances, sweeter than sugar, providing sweetness without calories. Sweeteners are mainly used as an aid in losing weight, preventing obesity and controlling blood sugar levels for diabetics. The objective of this study was to evaluate the carcinogenic potential of the sweeteners aspartame, sucralose, sodium saccharin and steviol glycoside, using the test for detection of epithelial tumor clones in Drosophila melanogaster. Larvae of 72 ± 4h, obtained from wts/TM3 female mated with mwh/mwh males, were treated for approximately 48h with different concentrations of aspartame (0.85, 1.7, 3.4, 6.8 or 13.6 mM ); sucralose (0.5, 1.25, 2.5, 5.0 or 10 mM); sodium saccharin (25; 50; 100; 200 or 400 mM) and steviol glycoside (2.5; 5.0; 10; 20 or 40 mM). Water (Reverse Osmosis) and doxorubicin (DXR 0.4 mM) were used as negative and positive controls, respectively. No statistically significant differences were observed (p > 0.05) in tumor frequencies in individuals treated with all concentrations of these sweeteners when compared to negative control. It was therefore concluded that, in these experimental conditions, aspartame, sucralose, sodium saccharin and steviol glycoside have no carcinogenic effect in D. melanogaster. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. An overview of the preclinical toxicity and potential carcinogenicity of sitaxentan (Thelin®), a potent endothelin receptor antagonist developed for pulmonary arterial hypertension.

    Science.gov (United States)

    Owen, Keith; Cross, David M; Derzi, Mazin; Horsley, Elizabeth; Stavros, Fiona L

    2012-10-01

    Sitaxentan (Thelin®), an endothelin receptor antagonist with a long duration of action and high specificity for the endothelin receptor A subtype, was used to treat pulmonary arterial hypertension. It was withdrawn from the market due to an idiosyncratic risk of drug-induced liver injury identified from emerging clinical trial data and clinical case reports. The preclinical safety profile of sitaxentan is presented, including single- and repeat-dose toxicity in mice, rats, and dogs and carcinogenicity in mice and rats. Sitaxentan-related adverse effects included coagulopathy in rats and dogs, increased serum alkaline phosphatase activity in mice and dogs, and hepatic hypertrophy in all species. Decreased albumin, erythrocyte count, hemoglobin concentration and hematocrit, and increased coagulation times and liver weight were also noted. These effects generally occurred at systemic exposures (AUC(0-24)) that were substantially greater than those seen in humans. Twice-daily (vs. once daily) dosing resulted in increased toxicity, which correlated with increased trough plasma sitaxentan concentrations. Sitaxentan appeared to have a low potential for testicular and hepatic toxicity and was not carcinogenic. These studies suggested that sitaxentan would have a reasonable margin of safety when used as directed in humans and supported a positive benefit:risk assessment at the time of marketing approval.

  19. Asphalt fume dermal carcinogenicity potential: II. Initiation-promotion assay of Type III built-up roofing asphalt.

    Science.gov (United States)

    Freeman, James J; Schreiner, Ceinwen A; Beazley, S; Burnett, Donald M; Clark, Charles R; Mahagaokar, Suneeta; Parker, Craig M; Stewart, Christopher W; Swanson, Mark S; Arp, Earl W

    2011-10-01

    Clark et al. (accepted for publication) reported that a sample of field-matched fume condensate from a Type III built-up roofing asphalt (BURA) resulted in a carcinogenic response in a mouse skin bioassay, with relatively few tumor-bearing animals, long tumor latency and chronic skin irritation. This mouse skin initiation/promotion study was conducted to assess possible mechanisms, i.e., genotoxic initiation vs. tumor promotion subsequent to repeated skin injury and repair. The same Type III BURA fume condensate sample was evaluated in groups of 30 male Crl:CD1® mice by skin application twice per week (total dose of 50 mg/week) for 2 weeks during the initiation phase and for 26 weeks during the promotion phase. Positive control substances were 7,12-dimethylbenz(a)anthracene (DMBA, 50 μg applied once) as an initiator and 12-O-tetradecanoyl-13-acetate (TPA, 5 μg, applied twice weekly) during the promotion phase. During the 6 months of study with the asphalt fume condensate, eight skin masses were observed when tested for initiation, five of which were confirmed microscopically to be benign squamous cell papillomas. Only two papillomas were observed when tested for promotion. There was no apparent relationship between skin irritation and tumor development in this study. These results are more indicative of genotoxicity rather than a non-genotoxic mode of action.

  20. Changes in rodent abundance and weather conditions potentially drive hemorrhagic fever with renal syndrome outbreaks in Xi'an, China, 2005-2012.

    Directory of Open Access Journals (Sweden)

    Huai-Yu Tian

    2015-03-01

    Full Text Available Increased risks for hemorrhagic fever with renal syndrome (HFRS caused by Hantaan virus have been observed since 2005, in Xi'an, China. Despite increased vigilance and preparedness, HFRS outbreaks in 2010, 2011, and 2012 were larger than ever, with a total of 3,938 confirmed HFRS cases and 88 deaths in 2010 and 2011.Data on HFRS cases and weather were collected monthly from 2005 to 2012, along with active rodent monitoring. Wavelet analyses were performed to assess the temporal relationship between HFRS incidence, rodent density and climatic factors over the study period. Results showed that HFRS cases correlated to rodent density, rainfall, and temperature with 2, 3 and 4-month lags, respectively. Using a Bayesian time-series Poisson adjusted model, we fitted the HFRS outbreaks among humans for risk assessment in Xi'an. The best models included seasonality, autocorrelation, rodent density 2 months previously, and rainfall 2 to 3 months previously. Our models well reflected the epidemic characteristics by one step ahead prediction, out-of-sample.In addition to a strong seasonal pattern, HFRS incidence was correlated with rodent density and rainfall, indicating that they potentially drive the HFRS outbreaks. Future work should aim to determine the mechanism underlying the seasonal pattern and autocorrelation. However, this model can be useful in risk management to provide early warning of potential outbreaks of this disease.

  1. Prostaglandin synthase-mediated metabolism of carcinogens and a potential role for peroxyl radicals as reactive intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Marnett, L.J. (Vanderbilt Univ. School of Medicine, Nashville, TN (USA))

    1990-08-01

    Prostaglandin-H synthase is unique among enzymes of the plant and animal kingdom in its ability to biosynthesize and metabolize hydroperoxides. Higher oxidation states of the peroxidase oxidize reducing substrates to electron-deficient derivatives that react with macromolecular nucleophiles. In the case of aromatic amines, the electron-deficient derivatives are mutagenic to bacterial and mammalian cells. {beta}-Dicarbonyl compounds and retinoic acid are oxidized to carbon-centered radicals that react with O{sub 2} to form peroxyl free radicals. Peroxyl radicals are the most stable oxy radicals and are able to diffuse some distance from the site of their generation. Peroxyl radicals are also formed during lipid peroxidation and in the reaction of polyunsaturated fatty acid hydroperoxides with metal complexes and metalloproteins. Peroxyl radicals epoxidize isolated doubled bonds of compounds such as 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP-7,8-diol); 3,4-dihydroxy-3,4-dihydrobenzo(a)anthracene; and aflatoxin B{sub 1}. The epoxide products represent the ultimate carcinogenic forms of the respective compounds. Techniques for quantitating the extent of peroxidase dependent or peroxyl radical-dependent metabolism in vivo make use of differences in the structure or stereochemistry of reactive intermediates formed by peroxidases relative to cytochromes P-450. Differences in the relative amounts of hydrolysis products and DNA adducts derived from anti- and syn-dihydrodiolepoxides following application of BP-7,8-diol to mouse skin in vivo indicate peroxyl radicals play a significant role in metabolism of BP-7,8-diol in uninduced animals.

  2. Carcinogens formed when Meat is Cooked

    Energy Technology Data Exchange (ETDEWEB)

    Felton, J S; Salmon, C P; Knize, M G

    2003-05-30

    Diet has been associated with varying cancer rates in human populations for many years, yet the causes of the observed variation in cancer patterns have not been adequately explained (Wynder et al. 1977). Along with the effect of diet on human cancer incidence is the strong evidence that mutations are the initiating events in the cancer process (Vogelstein et al. 1992). Foods, when heated, are a good source of genotoxic carcinogens that very likely are a cause for some of these events(Doll et al. 1981). These carcinogens fall into two chemical classes: heterocyclic aromatic amines (HAA) and polycyclic aromatic hydrocarbons (PAH). There is ample evidence that many of these compounds are complete carcinogens in rodents(El-Bayoumy et al. 1995; Ohgaki et al. 1991). Heterocyclic aromatic amines are among the most potent mutagenic substances ever tested in the Ames/Salmonella mutagenicity test (Wakabayashi et al. 1992). Both classes of carcinogen cause tumors in rodents at multiple sites, (El-Bayoumy et al. 1995; Ohgaki et al. 1991) many of which are common tumor sites in people on a Western diet. An HAA, PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), and a PAH, B[a]P (benzo[a]pyrene), of comparable carcinogenic potency caused mammary gland tumors in a feeding study in female rats (El-Bayoumy et al. 1995). In addition, PhIP has recently been shown to cause carcinomas in the prostate of the male rat (Shirai et al. 1997). Complementing the rodent cancer studies are numerous human case-control and prospective studies suggesting a relationship between overheated beef, chicken, and lamb, and cancer of the colon, breast, prostate, and stomach (Sinha et al. 1999; Ward et al. 1997; Zheng et al. 1998).

  3. Trypanosoma from rodents as potential source of infection in human-shaped landscapes of South-East Asia.

    Science.gov (United States)

    Pumhom, Pornpan; Morand, Serge; Tran, Annelise; Jittapalapong, Sathaporn; Desquesnes, Marc

    2015-03-15

    Reports of atypical human cases of Trypanosoma lewisi or T. lewisi-like and Trypanosoma evansi infections have increased in South-East Asia, urging to investigate the possible links between humans, animal reservoirs and habitats. We tested how habitat structure affects the infection by Trypanosoma species of common murine rodents, inhabiting human-dominated landscapes in South East Asia. For this, we used geo-referenced data of rodents investigated for Trypanosoma infection and land cover maps produced for seven study sites in Thailand, Cambodia and Lao PDR. High prevalence of infection by T. lewisi was observed in rodents living near human settlement and in areas with high cover of built-up habitat, while the infection of rodents by T. evansi was explained by increased landscape patchiness and high cover of rain-fed agriculture lands. These results suggest a likely role of wild rodents as reservoir and possible source of atypical human infection by animal trypanosomes.

  4. Carcinogenic potential of noxious emissions of diesel engines; Potencial cancerigeno de emisiones nocivas en motores a diesel

    Energy Technology Data Exchange (ETDEWEB)

    Romero Lopez, Alejandro F. [Universidad Nacional Autonoma de Mexico, Mexico, D. F. (Mexico)

    1992-12-31

    The carcinogenic effects of the solid particles of carbonaceous nature, generated during the combustion process in the diesel engines, has been a concern of public and private entities in the developed countries, specially during the two last decades. This paper includes a short revision of the recent and preceding publications, found in the technical bibliography. The engine manufacturing enterprises have carried out spectacular changes in the internal design of the diesel engines, to diminish as much as possible, the solid particle generation inside the engine itself. The effort can not come from one part only, also the fuel producing enterprises in developed countries have carried out substantial efforts to improve the fuels as well as the lubricants. The goal of this measures is to practically eliminate the sulfur content, specially in the fuel, since the formation of solid particles linearly depends, among other factors, of this noxious element content in the diesel fuel. Finally, a short discussion is included of some exhaust gases post-treatment systems, that seems to be unavoidable in order to attain the strict standards that for year 1994 and the following years have been established by the Environmental Protection Agency (EPA) of the USA. The Mexican legislation is also analyzed through the Normas Tecnicas Ecologicas (NTE) (Ecological Technical Standards), emitted by the Secretaria de Desarrollo Urbano y Ecologia (SEDUE), now Secretaria de Desarrolo Economico y Social (SEDESOL), simply to have a comparison reference with the international legislation. [Espanol] Los efectos cancerigenos de las particulas solidas de caracter carbonaceo, generadas durante el proceso de combustion de los motores diesel, ha sido preocupacion de organismos publicos y privados en los paises desarrollados, en especial durante las ultimas dos decadas. El trabajo incluye una revision breve de publicaciones recientes y anteriores, que se encuentran en la literatura tecnica. Las

  5. Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT)

    Science.gov (United States)

    Harada, Takanori; Takeda, Makio; Kojima, Sayuri; Tomiyama, Naruto

    2016-01-01

    Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p′-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT. PMID:26977256

  6. AI AND SAR APPROACHES FOR PREDICTING CHEMICAL CARCINOGENICITY: SURVEY AND STATUS REPORT

    Science.gov (United States)

    A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoin...

  7. AI AND SAR APPROACHES FOR PREDICTING CHEMICAL CARCINOGENICITY: SURVEY AND STATUS REPORT

    Science.gov (United States)

    A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoin...

  8. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis.

    Science.gov (United States)

    Hu, Zhiwei; Brooks, Samira A; Dormoy, Valérian; Hsu, Chia-Wen; Hsu, Hsue-Yin; Lin, Liang-Tzung; Massfelder, Thierry; Rathmell, W Kimryn; Xia, Menghang; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Brown, Dustin G; Prudhomme, Kalan R; Colacci, Annamaria; Hamid, Roslida A; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P; Woodrick, Jordan; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K; Lowe, Leroy; Jensen, Lasse; Bisson, William H; Kleinstreuer, Nicole

    2015-06-01

    One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential.

  9. Anti-hepatotoxic potential of Hedyotis corymbosa against D-galactosamine-induced hepatopathy in experimental rodents

    Institute of Scientific and Technical Information of China (English)

    Ramesh Kr Gupta; Rajnish Kr Singh; Sudhansu Ranjan Swain; Talib Hussain; Chandana Venkateswara Rao

    2012-01-01

    Objective: To evaluate hepatoprotective potential of the methanolic extract of Hedyotis corymbosa against D-galactosamine-induced hepatopathy in experimental animals. Methods: In the present study, in- vivo hepatoprotective effect of 50% methanolic extract of Hedyotis corymbosa (HCE, 100 and 200 mg/kg body weight) was evaluated using experimental models D-Galactosamine (D-GalN) (200 mg/kg, body weight i.p.) induced hepatotoxicity in experimental animals. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), γ-glutamyl transferase (γ-GT) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Results: Obtained results demonstrated that the treatment with HCE signi-cantly (P<0.05-P<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, HCE signi-cantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that HCE attenuated the hepatocellular necrosis and led to reduction of in ammatory cells in-ltration. Conclusions: The results of this study strongly indicate the protective effect of HCE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scienti-cally support its traditional use.

  10. Anti-ulcer and ulcer healing potentials of Musa sapientum peel extract in the laboratory rodents

    Directory of Open Access Journals (Sweden)

    Samuel Adetunji Onasanwo

    2013-01-01

    Full Text Available Background: This study investigated the anti-ulcer and ulcer healing potentials of the methanol extract of Musa sapientum peel in the laboratory rats. Materials and Methods: Methanol extract of the peels on Musa sapientum (MEMS was evaluated for its anti-ulcer using alcohol-induced, aspirin-induced, and pyloric ligation-induced models, and for its ulcer healing employing acetic acid-induced ulcer models in rats. Results: The findings from this experiment showed that MEMS (50, 100 and 200 mg/kg, b.w. anti-ulcer and ulcer healing activity (P ≤ 0.05 is dose-dependent. Also, MEMS exhibited healing of the ulcer base in all the treated groups when compared with the control group. Conclusion: The outcomes of this experiment revealed that the anti-ulcer effect of MEMS may be due to its anti-secretory and cyto-protective activity. The healing of the ulcer base might not be unconnected with basic fibroblast growth factors responsible for epithelial regeneration.

  11. Evaluation of anti-inflammatory potential of Nardostachys jatamansi rhizome in experimental rodents

    Directory of Open Access Journals (Sweden)

    Rajnish Kumar Singh

    2014-01-01

    Full Text Available Objective: To evaluate the anti-inflammatory effect of Nardostachys jatamansi (N. jatamansi rhizome against acute, subacute and chronic models of inflammation in experimental animals. Methods: N. jatamansi rhizome extract (150 and 300 mg/kg, p.o. and the reference drugs phenylbutazone (100 mg/kg, p.o. and acetylsalicylic acid (300 mg/kg, p.o. were evaluated using models for inflammation (autacoids induced hind paw oedema, formaldehyde induced hind paw oedema, carrageenin-induced paw oedema, cotton pellet granuloma and subcutaneous air pouch model. Results: In acute inflammation as produced by carrageenin 29.06% and 55.81%, by histamine 25.0% and 39.28%, by 5-hydroxytryptamine 21.37% and 36.95% and by prostaglandin E2- induced hind paw oedema 31.03% and 44.82% protection was observed. While in subacute antiinflammatory models using formaldehyde-induced hind paw oedema (after 1.5 h 13.88% and 33.33% and in chronic anti-inflammatory model using cotton pellet granuloma 7.4% and 17.58% protection from inflammation was observed. N. jatamansi rhizome extract also inhibited the inflammatory mediators (nitric oxide by 12.81% and 38.41%, by prostaglandin E2 12.58% and 47.82% while by TNF-α 13.51% and 41.89% produced in the pouch. Conclusions: The results of this study strongly indicate the protective effect of N. jatamansi rhizome extract against acute, subacute and chronic models of inflammation, which may be attributed to its anti-inflammatory potential.

  12. Evaluation of anti-inflammatory potential of Nardostachys jatamansi rhizome in experimental rodents

    Institute of Scientific and Technical Information of China (English)

    Rajnish Kumar Singh; Vaishali; Susanta Kumar Panda; Padala Narasimha Murthy; Ghanashyam Panigrahi; Pramod Kumar Sharma; Ramesh Kumar Gupta

    2014-01-01

    Objective: To evaluate the anti-inflammatory effect of Nardostachys jatamansi (N. jatamansi) rhizome against acute, subacute and chronic models of inflammation in experimental animals.Methods: N. jatamansi rhizome extract (150 and 300 mg/kg, p.o.) and the reference drugs phenylbutazone (100 mg/kg, p.o.) and acetylsalicylic acid (300 mg/kg, p.o.) were evaluated using models for inflammation (autacoids induced hind paw oedema, formaldehyde induced hind paw oedema, carrageenin-induced paw oedema, cotton pellet granuloma and subcutaneous air pouch model). Results: In acute inflammation as produced by carrageenin 29.06% and 55.81%, by histamine 25.0% and 39.28%, by 5-hydroxytryptamine 21.37% and 36.95% and by prostaglandin E2-induced hind paw oedema 31.03% and 44.82% protection was observed. While in subacute anti-inflammatory models using formaldehyde-induced hind paw oedema (after 1.5 h) 13.88% and 33.33% and in chronic anti-inflammatory model using cotton pellet granuloma 7.4% and 17.58%protection from inflammation was observed. N. jatamansi rhizome extract also inhibited the inflammatory mediators (nitric oxide by 12.81% and 38.41%, by prostaglandin E2 12.58% and 47.82%while by TNF-α 13.51% and 41.89%) produced in the pouch. Conclusions: The results of this study strongly indicate the protective effect of N. jatamansi rhizome extract against acute, subacute and chronic models of inflammation, which may be attributed to its anti-inflammatory potential.

  13. Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide (Final Report)

    Science.gov (United States)

    EPA has finalized its Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide. This assessment addresses the potential carcinogenicity from long-term inhalation exposure to ethylene oxide. Now final, this assessment updates the carcinogenicity information in EPA’s 1985 Hea...

  14. The development of improved and new in vitro assays for detecting the genotoxic and non-genotoxic carcinogenic potential of chemicals in the discovery phase of drug development

    NARCIS (Netherlands)

    Westerink, W.M.A.

    2011-01-01

    In drug development, toxicity is an important factor for attrition, resulting in a failure rate of 30%-40%. Hepatotoxicity, nephrotoxicity, cardiovascular safety, reproduction toxicity, developmental toxicity (teratogenicity), genotoxicity and carcinogenicity are the main causes for attrition in saf

  15. OVERVIEW OF DRINKING WATER MUTAGENICITY AND CARCINOGENICITY AND RISK FOR BLADDER CANCER

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroacetic acid and chlorite) are not carcinogenic-in either of 2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxici...

  16. The carcinogenicity of dietary acrylamide intake: A comparative discussion of epidemiological and experimental animal research

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Baars, B.-J.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2010-01-01

    Since 2002, it is known that the probable human carcinogen acrylamide is present in commonly consumed carbohydrate-rich foods, such as French fries and potato chips. In this review, the authors discuss the body of evidence on acrylamide carcinogenicity from both epidemiological and rodent studies, i

  17. Peroxisome Proliferator-activated Receptors as Potential Targets for Carcinogenic Activity of Polychlorinated Biphenyls: A Computational Perspective.

    Science.gov (United States)

    Sheikh, Ishfaq Ahmad; Khweek, Arwa Abu; Beg, Mohd Amin

    2016-11-01

    Polychlorinated biphenyls (PCBs) are ubiquitous environment-contaminating synthetic chemicals that have been associated with increased risk of hepatic cancer, melanoma, non-Hodgkin lymphoma and cancer of many other body organs. Structural binding analyses of PCB 77 and PCB 118 with peroxisome proliferator-activated receptors (PPARα, PPARβ/δ and PPARγ) was performed to predict the association of PCBs with potential disruption of PPAR signaling pathways. The crystal structures of human PPARα, PPARβ/δ and PPARγ were obtained from the Protein Data Bank. Structures of PCB 77 and PCB 118 were obtained from PubChem database. Docking was performed using glide (Schrodinger) induced fit docking (IFD) module. The PCB 77 and PCB 118 interacted with PPARα, PPARβ/δ and PPARγ showing an overlapping of 40-58% interacting amino acid residues with synthetic co-complex agonists of the three PPARs. The binding affinity was higher for PCB 118 than for PCB 77 during docking interactions with each of the three PPARs. The consistent commonality of interacting residues for PCB 77 and PCB 118 with co-complex synthetic agonists of the PPARs together with good binding affinity suggested that the PPAR signaling pathway is a potential target for toxicologic activity of PCBs. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Retrotransposon OV-RTE-1 from the carcinogenic liver fluke Opisthorchis viverrini: potential target for DNA-based diagnosis.

    Science.gov (United States)

    Thi Phung, Luyen; Loukas, Alex; Brindley, Paul J; Sripa, Banchob; Laha, Thewarach

    2014-01-01

    Infections by the fish-borne liver flukes Opisthorchis viverrini and Clonorchis sinensis can lead to bile duct cancer. These neglected tropical disease pathogens occur in East Asia, with O. viverrini primarily in Thailand and Laos and C. sinensis in Cambodia, Vietnam, and China. Genomic information about these pathogens holds the potential to improve disease treatment and control. Transcriptome analysis indicates that mobile genetic elements are active in O. viverrini, including a novel non-Long Terminal Repeat (LTR) retrotransposon. A consensus sequence of this element, termed OV-RTE-1, was assembled from expressed sequence tags and PCR amplified genomic DNA. OV-RTE-1 was 3330 bp in length, encoded 1101 amino acid residues and exhibited hallmark structures and sequences of non-LTR retrotransposons including a single open reading frame encoding apurinic-apyrimidinic endonuclease (EN) and reverse transcriptase (RT). Phylogenetic analyses confirmed that OV-RTE-1 was member of the RTE clade of non-LTR retrotransposons. OV-RTE-1 is the first non-LTR retrotransposon characterized from the trematode family Opisthorchiidae. Sequences of OV-RTE-1 were targeted to develop a diagnostic tool for detection of infection by O. viverrini. PCR specific primers for detection of O. viverrini DNA showed 100% specificity and sensitivity for detection of as little as 5 fg of O. viverrini DNA whereas the PCR based approach showed 62% sensitivity and 100% specificity with clinical stool samples. The OV-RTE-1 specific PCR could be developed as a molecular diagnostic for Opisthorchis infection targeting parasite eggs in stool samples, especially in regions of mixed infection of O. viverrini and/or C. sinensis and minute intestinal flukes.

  19. Environmental occurrence, origin, physical and geochemical properties, and carcinogenic potential of erionite near San Miguel de Allende, Mexico.

    Science.gov (United States)

    Ortega-Guerrero, M Adrián; Carrasco-Núñez, Gerardo

    2014-06-01

    Detailed geologic surveys and different microscopic and analytical techniques were conducted near Tierra Blanca de Abajo where lung cancer and malignant mesothelioma (MM) are the primary causes of death. Results show that erionite-K occurs as a diagenetic product in altered Oligocene-Miocene rhyolitic tuffs. The microscopic structure of erionite minerals shows concentrations of individual fibers in the range of 0.14-0.547 μm in diameter and 2.81-50 μm in length, with a few "bundles" about 0.2-2.5 μm wide by 10-50 μm long. Chemical properties of erionite show Si/Al in the range of 3.23-3.58 (at.%) and T Si in the range of 0.76-0.78 (at.%). Potassium is the dominant cation (K > Ca > Mg > Fe). Associated minerals are heulandite, clinoptilolite, quartz, sanidine, anorthite, smectite and opal. This mineral assemblage formed in the lower part of an open catchment, where bicarbonate-rich (T > 30 °C, pH > 8) groundwater discharge conditions prevailed in the past. The physical and chemical characteristics of erionite near San Miguel de Allende are similar to those of erionite from the Cappadocian region of Turkey where erionite is associated with MM. The presence of erionite and the type of respiratory diseases that occur in the village strongly suggest the need for detailed health-based studies in the region. Pliocene-Holocene fine-grain deposits, used in the past for the construction of adobe-houses and exposed in recreational areas, also contain erionite associated with erosion and alluvial transport from the rhyolitic tuffs, potentially affecting more than 13 villages located downstream toward the Allende Dam.

  20. Protection by dietary compounds against mutation in a transgenic rodent.

    Science.gov (United States)

    de Boer, J G

    2001-11-01

    One of the most relevant biomarkers of genotoxicity and, potentially, carcinogenesis is the occurrence of mutations. Data indicate that carcinogens are highly specific with regard to their target tissue in inducing both tumors and mutations. This specificity may reflect the dependence on tissue-specific metabolic activation, the organ-specific environment or both. Ideally, therefore, mutation should be determined in a real animal rather than in a cell culture system. The lacI transgenic rodent model provides such a system. We have used this model to investigate tissue, species and sex specificity of mutation induced by selected dietary carcinogens and to examine how some compounds may alter the induction of mutation. We have studied mutation using several chemicals, including the dietary heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the environmentally important aromatic hydrocarbon benzo[a]pyrene and the food contaminant aflatoxin B1. We have shown that the mutagenic potency of these chemicals can be modulated by other dietary compounds, including green tea and conjugated linoleic acid, and the dioxin 2,3,7,8-tetrachlorodibenzo[b,e][1,4]dioxin (TCDD). These results demonstrate that the lacI transgenic rodent is a useful model for the study of chemoprevention in vivo.

  1. Improving prediction of carcinogenicity to reduce, refine, and replace the use of experimental animals.

    Science.gov (United States)

    Bourcier, Todd; McGovern, Tim; Stavitskaya, Lidiya; Kruhlak, Naomi; Jacobson-Kram, David

    2015-03-01

    Cancer risk assessment of new pharmaceuticals is crucial to protect public health. However, clinical trials lack the duration needed to clearly detect drug-related tumor emergence, and biomarkers suggestive of increased cancer risk from a drug typically are not measured in clinical trials. Therefore, the carcinogenic potential of a new pharmaceutical is extrapolated predominately based on 2-y bioassays in rats and mice. A key drawback to this practice is that the results are frequently positive for tumors and can be irrelevant to human cancer risk for reasons such as dose, mode of action, and species specificity. Alternative approaches typically strive to reduce, refine, and replace rodents in carcinogenicity assessments by leveraging findings in short-term studies, both in silico and in vivo, to predict the likely tumor outcome in rodents or, more broadly, to identify a cancer risk to patients. Given the complexities of carcinogenesis and the perceived impracticality of assessing risk in the course of clinical trials, studies conducted in animals will likely remain the standard by which potential cancer risks are characterized for new pharmaceuticals in the immediate foreseeable future. However, a weight-of-evidence evaluation based on short-term toxicologic, in silico, and pharmacologic data is a promising approach to identify with reasonable certainty those pharmaceuticals that present a likely cancer risk in humans and, conversely, those that do not present a human cancer risk.

  2. Detection of genotoxic and non-genotoxic carcinogens in Xpc{sup −/−}p53{sup +/−} mice

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Joost P.M. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); Speksnijder, Ewoud N. [Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); Kuiper, Raoul V. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht (Netherlands); Salvatori, Daniela C.F. [Leiden University Medical Center, Central Animal Facility, Leiden (Netherlands); Schaap, Mirjam M. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); Maas, Saskia [Leiden University Medical Center, Central Animal Facility, Leiden (Netherlands); Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Steeg, Harry van, E-mail: Harry.van.Steeg@rivm.nl [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands)

    2013-01-15

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  3. Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

    Directory of Open Access Journals (Sweden)

    Kwon JY

    2014-12-01

    Full Text Available Jee Young Kwon,1,* Preeyaporn Koedrith,2,* Young Rok Seo1 1Department of Life Science, Institute of Environmental Medicine, Dongguk University, Seoul, Republic of Korea; 2Faculty of Environment and Resource Studies, Mahidol University, Phuttamonthon District, NakhonPathom, Thailand *These authors contributed equally to this work and should be considered as co-first authors Abstract: Engineered nanoparticles (NPs are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. Keywords: carcinogenicity, exposure assessment, genotoxicity, nanoparticles, risk evaluation

  4. Search for Internal Cancers in Mice Tattooed with Inks of High Contents of Potential Carcinogens: A One-Year Autopsy Study of Red and Black Tattoo Inks Banned in the Market.

    Science.gov (United States)

    Sepehri, Mitra; Lerche, Catharina M; Hutton Carlsen, Katrina; Serup, Jørgen

    2017-01-01

    Tattoo ink stock products often contain potential carcinogens, which on large-scale population exposure may be clinically relevant. The aim of this autopsy study in mice was to screen major organs for clinical and subclinical cancers. Mice were tattooed on their backs. In total, 48 mice were included and divided into 4 groups; 11 mice tattooed black, 10 tattooed red, and 5 mice serving as untreated controls. A group of 22 mice with black tattoos and exposed to ultraviolet radiation (UVR) were also studied. The black and red inks were both stock products banned on the Danish market due to the measured contents of potential carcinogens; benzo(a)pyrene and 2-anisidine, respectively. The mice were housed for 1 year after tattooing, and autopsy study on internal organs was performed. Tissue samples were systematically taken from major organs for screening of subclinical changes, not detected by visual examination. Any observed deviation from normal structure was subject to biopsy and light microscopy. All mice survived the 1-year observation period. Autopsy revealed no macroscopic signs of cancer. Microscopic search of internal organs showed no subclinical or clinical cancer. Despite extensive tattoos with 2 banned inks, the long-term observation in mice showed no internal cancers nor was the combination of carcinogen and UVR associated with cancer. Lack of observed malignancy might be explained by the fact that tattooing is only a single dose exposure. Registered data on carcinogens relies on repeated or chronic exposures. The study does not support the hypothesis that tattooing causes cancer. © 2017 S. Karger AG, Basel.

  5. An integrated approach for prospectively investigating a mode-of-action for rodent liver effects

    Energy Technology Data Exchange (ETDEWEB)

    LeBaron, Matthew J., E-mail: MJLeBaron@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Geter, David R., E-mail: dave.geter@gmail.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Rasoulpour, Reza J. [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Gollapudi, B. Bhaskar, E-mail: BBGollapudi@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Thomas, Johnson, E-mail: JThomas4@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Murray, Jennifer, E-mail: AMurray@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Kan, H. Lynn, E-mail: HLKan@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Wood, Amanda J., E-mail: AJWood@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Elcombe, Cliff, E-mail: CliffElcombe@cxrbiosciences.com [CXR Biosciences, 2 James Lindsay Place, Dundee Technopole, Dundee, DD1 5JJ, Scotland (United Kingdom); Vardy, Audrey, E-mail: audrey_vardy@europe.bd.com [CXR Biosciences, 2 James Lindsay Place, Dundee Technopole, Dundee, DD1 5JJ, Scotland (United Kingdom); McEwan, Jillian, E-mail: jillian.mcewan@rtmcewan.co.uk [CXR Biosciences, 2 James Lindsay Place, Dundee Technopole, Dundee, DD1 5JJ, Scotland (United Kingdom); Terry, Claire, E-mail: CTerry@dow.com [Dow AgroSciences, Abingdon, Oxfordshire (United Kingdom); Billington, Richard, E-mail: RBillington@dow.com [Dow AgroSciences, Abingdon, Oxfordshire (United Kingdom)

    2013-07-15

    Registration of new plant protection products (e.g., herbicide, insecticide, or fungicide) requires comprehensive mammalian toxicity evaluation including carcinogenicity studies in two species. The outcome of the carcinogenicity testing has a significant bearing on the overall human health risk assessment of the substance and, consequently, approved uses for different crops across geographies. In order to understand the relevance of a specific tumor finding to human health, a systematic, transparent, and hypothesis-driven mode of action (MoA) investigation is, appropriately, an expectation by the regulatory agencies. Here, we describe a novel approach of prospectively generating the MoA data by implementing additional end points to the standard guideline toxicity studies with sulfoxaflor, a molecule in development. This proactive MoA approach results in a more robust integration of molecular with apical end points while minimizing animal use. Sulfoxaflor, a molecule targeting sap-feeding insects, induced liver effects (increased liver weight due to hepatocellular hypertrophy) in an initial palatability probe study for selecting doses for subsequent repeat-dose dietary studies. This finding triggered the inclusion of dose-response investigations of the potential key events for rodent liver carcinogenesis, concurrent with the hazard assessment studies. As predicted, sulfoxaflor induced liver tumors in rats and mice in the bioassays. The MoA data available by the time of the carcinogenicity finding supported the conclusion that the carcinogenic potential of sulfoxaflor was due to CAR/PXR nuclear receptor activation with subsequent hepatocellular proliferation. This MoA was not considered to be relevant to humans as sulfoxaflor is unlikely to induce hepatocellular proliferation in humans and therefore would not be a human liver carcinogen. - Highlights: • We prospectively generated MoA data into standard guideline toxicity studies. • A proactive MoA approach

  6. Analysis of genotoxicity and the carcinogenic mode of action for ortho-phenylphenol.

    Science.gov (United States)

    Brusick, David

    2005-06-01

    Ortho-phenylphenol (OPP) and its sodium salt (SOPP) are commercial products that have wide human exposure and have been shown in several studies to be rodent carcinogens. Genetic toxicology data were assessed in an attempt to understand the carcinogenic mode of action of OPP and SOPP. More than 130 studies were evaluated to determine if OPP, SOPP, or any of their enzymatic or nonenzymatic breakdown products react directly with DNA to induce mutation, changes in chromosome structure or number, DNA repair, or nonspecific DNA damage including strand breakage or covalent binding. The genotoxicity databases for OPP and SOPP are not only large but heterogeneous, requiring weight-of-evidence methods to arrive at a conclusion regarding their genotoxic properties and potential. Evidence derived from the available studies leads to the conclusion that study results showing OPP/SOPP directly interacting with DNA are equivocal. Clastogenicity was the most consistent type of genetic toxicity produced by OPP/SOPP (and their break-down products) and was consistently associated with other intracellular preneoplastic toxicity produced at super-threshold concentrations. The weight of evidence from the combined database supports the hypothesis that OPP/SOPP-induced DNA damage is a threshold-dependent response associated with target tissue toxicity, most likely induced by their breakdown products phenylhydroquinone and phenylbenzoquinone. It is possible that this threshold-dependent clastogenicity could contribute to the carcinogenic mode of action for OPP or SOPP.

  7. Beryllium: genotoxicity and carcinogenicity.

    Science.gov (United States)

    Gordon, Terry; Bowser, Darlene

    2003-12-10

    Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

  8. Best practices for clinical pathology testing in carcinogenicity studies.

    Science.gov (United States)

    Young, Jamie K; Hall, Robert L; O'Brien, Peter; Strauss, Volker; Vahle, John L

    2011-02-01

    The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) convened a Clinical Pathology in Carcinogenicity Studies Working Group to recommend best practices for inclusion of clinical pathology testing in carcinogenicity studies. Regulatory guidance documents and literature were reviewed, and veterinary pathologists from North America, Japan, and Europe were surveyed regarding current practices, perceived value, and recommendations for clinical pathology testing in carcinogenicity studies. For two-year rodent carcinogenicity studies, the Working Group recommends that clinical pathology testing be limited to collection of blood smears at scheduled and unscheduled sacrifices to be examined only if indicated to aid in the diagnosis of possible hematopoietic neoplasia following histopathologic evaluation. Additional clinical pathology testing is most appropriately used to address specific issues from prior toxicity studies or known test article-related class effects. Inadequate data were available to make a recommendation concerning clinical pathology testing for alternative six-month carcinogenicity assays using genetically modified mice, although the Working Group suggests that it may be appropriate to use the same approach as for two-year carcinogenicity studies since the study goal is the same.

  9. Report on carcinogens monograph on 1-bromopropane.

    Science.gov (United States)

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in

  10. Techniques for carcinogenicity studies.

    Science.gov (United States)

    Weisburger, E K

    1981-09-01

    Short-term tests to detect genetic, chromosomal, or DNA damage are now required by regulatory agencies for any new compound proposed for commercial production. Furthermore, full-scale carcinogenicity tests may be required for certain compounds. In this circumstance, the compound-related factors including stability, purity, physical properties, and chemical structure and reactivity must be considered. Animal factors include species and strain of test animal, route of administration, age, sex, diet, and spontaneous tumor incidence. A team of qualified investigators with experience in various disciplines is required to conduct the studies properly. Quality control measures and adherence to the code of good laboratory practice are also necessary during all phases of the study. The investment in a carcinogenicity study therefore becomes fairly substantial in terms of both time and money.

  11. Food derived carcinogenic amnoimidazoazaarenes

    DEFF Research Database (Denmark)

    Frandsen, Henrik

    Carcinogenic aminoimidazoazaarenes are formed during cooking of meat and fish. Important factors for the formation of these compounds are meat type, cooking temperature and time. The compounds are genotoxic in bacterial and mammalian cells. In animal feeding studies the compounds tested so far we...... of the exocyclic amino group. Estimations of human cancer risk have indicated that ingestion of food containing aminoimidazoazaarenes are of importance....

  12. [Leather azo dyes: mutagenic and carcinogenic risks].

    Science.gov (United States)

    Clonfero, E; Venier, P; Granella, M; Levis, A G

    1990-01-01

    The paper reviews the carcinogenicity and mutagenicity data on azo dyes used in the leather industry. Two water soluble benzidine-based dyes were classified as "probably carcinogenic to humans" by the International Agency for Research on Cancer (IARC). No other dyes have been evaluated by the IARC. Of the 48 azo dyes assayed in the Salmonella/microsome test, 20 gave positive results. Attention is drawn to the important role of the in vivo metabolism of azo compounds, which includes a preliminary reduction of the azo bonds and subsequent release of the aromatic amines of the dye. A useful assay (Prival test) for evaluating the mutagenic properties of azo dyes involves a reductive step that permits the release of any genotoxic agents present in the compounds. A list of leather azo dyes is furnished that are considered as potentially harmful due to the presence of a carcinogenic aromatic amine (benzidine, p-aminobenzene and derivatives) in their formulae.

  13. In Silico Methods for Carcinogenicity Assessment.

    Science.gov (United States)

    Golbamaki, Azadi; Benfenati, Emilio

    2016-01-01

    Screening compounds for potential carcinogenicity is of major importance for prevention of environmentally induced cancers. A large sequence of alternative predictive models, ranging from short-term biological assays (e.g. mutagenicity tests) to theoretical models, have been attempted in this field. Theoretical approaches such as (Q)SAR are highly desirable for identifying carcinogens, since they actively promote the replacement, reduction, and refinement of animal tests. This chapter reports and describes some of the most noted (Q)SAR models based on the human expert knowledge and statistically approach, aiming at predicting the carcinogenicity of chemicals. Additionally, the performance of the selected models has been evaluated and the results are interpreted in details by applying these prediction models to some pharmaceutical molecules.

  14. Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds.

    Science.gov (United States)

    Behl, Mamta; Stout, Matthew D; Herbert, Ronald A; Dill, Jeffrey A; Baker, Gregory L; Hayden, Barry K; Roycroft, Joseph H; Bucher, John R; Hooth, Michelle J

    2015-07-03

    Occupational exposure to cobalt is of widespread concern due to its use in a variety of industrial processes and the occurrence of occupational disease. Due to the lack of toxicity and carcinogenicity data following exposure to cobalt, and questions regarding bioavailability following exposure to different forms of cobalt, the NTP conducted two chronic inhalation exposure studies in rats and mice, one on soluble cobalt sulfate heptahydrate, and a more recent study on insoluble cobalt metal. Herein, we compare and contrast the toxicity profiles following whole-body inhalation exposures to these two forms of cobalt. In general, both forms were genotoxic in the Salmonella T98 strain in the absence of effects on micronuclei. The major sites of toxicity and carcinogenicity in both chronic inhalation studies were the respiratory tract in rats and mice, and the adrenal gland in rats. In addition, there were distinct sites of toxicity and carcinogenicity noted following exposure to cobalt metal. In rats, carcinogenicity was observed in the blood, and pancreas, and toxicity was observed in the testes of rats and mice. Taken together, these findings suggest that both forms of cobalt, soluble and insoluble, appear to be multi-site rodent carcinogens following inhalation exposure. Published by Elsevier Ireland Ltd.

  15. The comet assay with multiple mouse organs: comparison of comet assay results and carcinogenicity with 208 chemicals selected from the IARC monographs and U.S. NTP Carcinogenicity Database.

    Science.gov (United States)

    Sasaki, Y F; Sekihashi, K; Izumiyama, F; Nishidate, E; Saga, A; Ishida, K; Tsuda, S

    2000-11-01

    as genotoxic (Ames test-positive) and putative nongenotoxic (Ames test-negative) carcinogens. The Ames test is generally used as a first screening method to assess chemical genotoxicity and has provided extensive information on DNA reactivity. Out of 208 chemicals studied, 117 are Ames test-positive rodent carcinogens, 43 are Ames test-negative rodent carcinogens, and 30 are rodent noncarcinogens (which include both Ames test-positive and negative noncarcinogens). High positive response ratio (110/117) for rodent genotoxic carcinogens and a high negative response ratio (6/30) for rodent noncarcinogens were shown in the comet assay. For Ames test-negative rodent carcinogens, less than 50% were positive in the comet assay, suggesting that the assay, which detects DNA lesions, is not suitable for identifying nongenotoxic carcinogens. In the safety evaluation of chemicals, it is important to demonstrate that Ames test-positive agents are not genotoxic in vivo. This assay had a high positive response ratio for rodent genotoxic carcinogens and a high negative response ratio for rodent genotoxic noncarcinogens, suggesting that the comet assay can be used to evaluate the in vivo genotoxicity of in vitro genotoxic chemicals. For chemicals whose in vivo genotoxicity has been tested in multiple organs by the comet assay, published data are summarized with unpublished data and compared with relevant genotoxicity and carcinogenicity data. Because it is clear that no single test is capable of detecting all relevant genotoxic agents, the usual approach should be to carry out a battery of in vitro and in vivo tests for genotoxicity. The conventional micronucleus test in the hematopoietic system is a simple method to assess in vivo clastogenicity of chemicals. Its performance is related to whether a chemical reaches the hematopoietic system. Among 208 chemicals studied (including 165 rodent carcinogens), 54 rodents carcinogens do not induce micronuclei in mouse hematopoietic system

  16. Protein adducts of the prostate carcinogen PhIP in children

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence Livermore National Laboratory

    2004-02-20

    Prostate cancer is the second leading cause of cancer death in men in the United States. few epidemiology studies have indicated that exposure to PhIP, a rodent prostate carcinogen formed in meat during cooking, may be an important risk factor for prostate cancer in humans. Therefore, a highly sensitive biomarker assay is urgently needed to clarify the role of PhIP in prostate cancer. The goal of this project is to develop an assay that can be used to more accurately quantify human exposure to PhIP and potential prostate cancer risk. Our hypothesis is that an Accelerator Mass Spectrometry-based method can be developed to measure protein adducts of PhIP in the blood of humans. This will provide a measure of the internal dose, as well as the capacity for carcinogen bioactivation to a form that can initiate the cancer process. Towards this goal, we have characterized an adduct formed by PhIP in vitro with the amino acid cysteine. This adduct should provide a biomarker of dietary PhIP exposure and potential prostate cancer risk that could be used to identify individuals for prevention and for monitoring the effect chemoprevention strategies.

  17. Science, politics, and health in the brave new world of pharmaceutical carcinogenic risk assessment: technical progress or cycle of regulatory capture?

    Science.gov (United States)

    Abraham, John; Ballinger, Rachel

    2012-10-01

    The carcinogenicity (cancer-inducing potential) of pharmaceuticals is an important risk factor for health when considering whether thousands of patients on drug trials or millions/billions of consumers in the marketplace should be exposed to a new drug. Drawing on fieldwork involving over 50 interviews and documentary research spanning 2002-2010 in Europe and the US, and on regulatory capture theory, this article investigates how the techno-regulatory standards for carcinogenicity testing of pharmaceuticals have altered since 1998. It focuses on the replacement of long-term carcinogenicity tests in rodents (especially mice) with shorter-term tests involving genetically-engineered mice (GEM). Based on evidence regarding financial/organizational control, methodological design, and interpretation of the validation and application of these new GEM tests, it is argued that regulatory agencies permitted the drug industry to shape such validation and application in ways that prioritized commercial interests over the need to protect public health. Boundary-work enabling industry scientists to define some standards of public-health policy facilitated such capture. However, as the scientific credibility of GEM tests as tools to protect public health by screening out carcinogens became inescapably problematic, a regulatory resurgence, impelled by reputational concerns, exercised more control over industry's construction and use of the tests, The extensive problems with GEM tests as public-health protective regulatory science raises the spectre that alterations to pharmaceutical carcinogenicity-testing standards since the 1990s may have been boundary-work in which the political project of decreasing the chance that companies' products are defined as carcinogenic has masqueraded as techno-science.

  18. The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

    NARCIS (Netherlands)

    van Herwaarden, AE; Jonker, JW; Wagenaar, E; Brinkhuis, RF; Schellens, JHM; Beijnen, JH; Schinkel, AH

    2003-01-01

    The food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine found in various protein containing foods. PhIP is mutagenic and carcinogenic in rodents, inducing lymphomas in mice and colon, mammary and prostate carcinomas in rats. It has also been

  19. Rodents And Other Gnawers.

    Science.gov (United States)

    Naturescope, 1986

    1986-01-01

    Presents information about rodents and lagomorphs, including definitions and the characteristics of these animals. Contains teaching activities such as "Habitats for Hoppers,""Cartoon Gnawers," and "The Great Rodent Expedition." Reproducible handouts for two of the activities are provided. (TW)

  20. Critical factors in assessing risk from exposure to nasal carcinogens.

    Science.gov (United States)

    Bogdanffy, M S; Mathison, B H; Kuykendall, J R; Harman, A E

    1997-10-31

    Anatomical, physiological, biochemical and molecular factors that contribute to chemical-induced nasal carcinogenesis are either largely divergent between test species and humans, or we know very little of them. These factors, let alone the uncertainty associated with our knowledge gap, present a risk assessor with the formidable task of making judgments about risks to human health from exposure to chemicals that have been identified in rodent studies to be nasal carcinogens. This paper summarizes some of the critical attributes of the hazard identification and dose-response aspects of risk assessments for nasal carcinogens that must be accounted for by risk assessors in order to make informed decisions. Data on two example compounds, dimethyl sulfate and hexamethylphosphoramide, are discussed to illustrate the diversity of information that can be used to develop informed hypotheses about mode of action and decisions on appropriate dosimeters for interspecies extrapolation. Default approaches to interspecies dosimetry extrapolation are described briefly and are followed by a discussion of a generalized physiologically based pharmacokinetic model that, unlike default approaches, is flexible and capable of incorporating many of the critical species-specific factors. Recent advancements in interspecies nasal dosimetry modeling are remarkable. However, it is concluded that without the development of research programs aimed at understanding carcinogenic susceptibility factors in human and rodent nasal tissues, development of plausible modes of action will lag behind the advancements made in dosimetry modeling.

  1. An estimation of the carcinogenic risk associated with the intake of multiple relevant carcinogens found in meat and charcuterie products.

    Science.gov (United States)

    Hernández, Ángel Rodríguez; Boada, Luis D; Almeida-González, Maira; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valeron, Pilar F; Camacho, María; Zumbado, Manuel; Henríquez-Hernández, Luis A; Luzardo, Octavio P

    2015-05-01

    Numerous epidemiological studies have demonstrated a link between excessive meat consumption and the incidence of various cancers, especially colorectal cancer, and it has been suggested that environmental carcinogens present in meat might be related to the increased risk of cancer associated with this food. However, there are no studies evaluating the carcinogenic potential of meat in relation to its content of carcinogens. Our purpose was to emphasize the relevance of environmental carcinogens existing in meat as a determinant of the association between cancer and meat consumption. Because within Europe, Spain shows high consumption of meat and charcuterie, we performed this study focusing on Spanish population. Based on the preferences of consumers we acquired 100 samples of meat and charcuterie that reflect the variety available in the European market. We quantified in these samples the concentration of 33 chemicals with calculated carcinogenic potential (PAHs, organochlorine pesticides, and dioxin-like PCBs). The carcinogenic risk of these contaminants was assessed for each food using a risk ratio based on the current consumption of meat and charcuterie and the maximum tolerable intake of these foods depending on the level of contamination by the carcinogens they contain. Our results indicate that the current consumption of beef, pork, lamb, chicken, and "chorizo", represents a relevant carcinogenic risk for consumers (carcinogenic risk quotient between 1.33 and 13.98). In order to reduce carcinogenic risk, the study population should halve the monthly consumption of these foods, and also not to surpass the number of 5 servings of beef/pork/chicken (considered together). Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.

    Science.gov (United States)

    Laino, Carlos Horacio; Garcia, Pilar; Podestá, María Fernanda; Höcht, Christian; Slobodianik, Nora; Reinés, Analía

    2014-10-01

    We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014.

  3. [Application of genetic diversity in the researches on rodents].

    Science.gov (United States)

    Liu, Zhu; Yang, Chun-Wen; Xu, Yan-Chun; Jin, Zhi-Min; Ma, Jian-Zhang

    2014-02-01

    Genetic diversity is the base of the species diversity and ecosystem diversity, and also the foundation for biological evolution and species differentiation. Furthermore, genetic diversity is important evidence for evaluation of biological resources of nature. The genetic diversity data from a wide variety of rodents have many complex applications. We summarized the application of rodent prevention, the origin and differentiation including evolutionary history of rodents, the potential adaptation of rodents, the dynamics of population and regulatory mechanisms, and the conservation biology of rodents. Researches in the future should focus on the systematic study on the relationships between population dynamics and genetic diversity, and long-term monitoring of genetic diversity of rodents.

  4. Aging potentiates the acute and chronic neurological symptoms of pyrithiamine-induced thiamine deficiency in the rodent.

    Science.gov (United States)

    Pitkin, S R; Savage, L M

    2001-03-15

    The present study aimed to assess the role of advanced age in the development and manifestation of thiamine deficiency using an animal model of Wernicke-Korsakoff syndrome (WKS). Interactions between pyrithiamine-induced thiamine deficiency (PTD) and age were examined relative to working memory impairment and neuropathology in Fischer 344 rats. Young (2-3 months) and aged (22-23 months) F344 rats were assigned to one of two treatment conditions: PTD or pair-fed control (PF). Rats in the former group were further divided into three groups according to duration of PTD treatment. Working memory was assessed with an operant matching-to-position (MTP) task; after testing, animals were sacrificed and both gross and immunocytochemical measures of brain pathology were obtained. Aged rats exhibited acute neurological disturbances during the PTD treatment regime earlier than did young rats, and also developed more extensive neuropathology with a shorter duration of PTD. Aged rats displayed increased brain shrinkage (smaller frontal cortical and callosal thickness) as well as enhanced astrocytic activity in the thalamus and a decrease in ChAT-positive cell numbers in the medial septum; the latter two measures of neuropathology were potentiated by PTD. In both young and aged rats, and to a greater degree in the latter group, PTD reduced thalamic volume. Behaviorally, aged rats displayed impaired choice accuracy on the delayed MTP task. Regardless of age, rats with lesions centered on the internal medullary lamina of the thalamus also displayed impaired choice accuracy. Moreover, increased PTD treatment duration led to increased response times on the delayed MTP task. These results suggest that aging does indeed potentiate the neuropathology associated with experimental thiamine deficiency, supporting an age coupling hypothesis of alcohol-related neurological disorders.

  5. To investigate antihyperglycemic and antihyperlipidemic potential of safrole in rodents by in-vivo and in-vitro study.

    Science.gov (United States)

    Rani, S; Sharma, S; Kumar, S

    2014-06-01

    In the present investigation anti-diabetic and in-vitro antioxidant potential of safrole were evaluated (100 and 200 mg/kg p.o.) in acute and chronic Streptozotocin-nicotinamide (STZ) induced antihyperglycemic rat model. The oral administration of safrole for 30 days affects the level of blood glucose, glycosylated hemoglobin (HbA1C), total cholesterol (TC), triglycerides (TG), phospholipids, high density lipoprotein (HDL), body weight, insulin level, liver glycogen content, antioxidant parameters, lipase, α-amylase in normal and STZ induced diabetic rats. The oral administration of safrole at dose 100 & 200 mg/kg p.o. significantly improve the diabetic condition in Streptozotocin-induced diabetic rats. In enzymatic assay, the IC50 value of the safrole for α-amylase and lipase was found to be 702.78 and 861.35 μg/ml respectively which was found comparable with the standard drug (ascorbic acid) as 252.12 μg/ml. Further studies can be performed on safrole for mechanistic and toxicological aspects so that it can be investigated as a new substance for the management of various diseases.

  6. Examination of the potential genotoxicity of pure capsaicin in bacterial mutation, chromosome aberration, and rodent micronucleus tests.

    Science.gov (United States)

    Proudlock, Raymond; Thompson, Crista; Longstaff, Eric

    2004-01-01

    There is widespread dietary exposure to capsaicin in the form of chili peppers, while capsaicin's analgesic qualities have led to increased use of a topical herbal remedy in various impure forms. Most recently, injection of pure capsaicin has been proposed as a means of relieving a variety of debilitating diseases, in which case tissues would receive relatively high and direct exposure. The purpose of the present study, where a series of standard assays were performed in accordance with the Organisation for Economic Cooperation and Development guidance, was to clarify earlier conflicting reports concerning potential genotoxicity of capsaicin prior to administering it to patients in an injectable form. The results confirm the absence of genotoxic activity of high-purity capsaicin in the bacterial mutation and chromosome aberration tests. In addition, no evidence of cytotoxicity or genotoxicity was seen in the rat bone marrow micronucleus test, where systemic exposure to pure capsaicin was achieved using the subcutaneous route and a rising dose toleration protocol. It is concluded that pure capsaicin is not active in the standard battery of genotoxicity assays recommended by the International Conference on Harmonisation for evaluation of new medicines; earlier reported in vitro genotoxic activity is probably associated with mutagenic impurities in commercial grades of the material.

  7. Antimalarial potential of China 30 and Chelidonium 30 in combination therapy against lethal rodent malaria parasite: Plasmodium berghei.

    Science.gov (United States)

    Rajan, Aswathy; Bagai, Upma

    2013-05-07

    Homeopathy is a therapeutic method based on the application of similia principle, utilizing ultra-low doses of medicinal substances made from natural products. The present study has been designed to evaluate the efficacy of Cinchona officinalis (Chin.) 30C and Chelidonium majus (Chel.) 30C in combination therapy against lethal murine malaria. Five groups having twelve BALB/c mice each were administered orally with 0.2 ml/mouse/day of different drugs, and their antimalarial potential was evaluated by Peter's 4-day test. The combination of Chin. 30 and Chel. 30 exhibited complete parasite clearance by the 28th day post-inoculation which was similar to the positive control [artesunate (4 mg/kg)+sulphadoxine-primethamine (1.2 mg/kg)] group. Both the groups exhibited enhanced mean survival time (MST) 28±0 days,whereas, the mice of infected control group survived up to 7.6±0.4 days only. The preventive and curative activities of the combination in comparison to the positive controls [pyrimethamine (1.2 mg/Kg) and chloroquine (20 mg/Kg), respectively] were also evaluated. The combination had a significant preventive activity (p<0.0005), with 89.2% chemosuppression which was higher than the standard drug, pyrimethamine (83.8%). It also showed a moderate curative activity with complete clearance of parasite in 50% of surviving mice, and enhancing the MST of mice up to 26.8±2.8 days. These findings point to the significant antiplasmodial efficacy of the combination of these homeopathic drugs against Plasmodium berghei.

  8. Acrylonitrile: a suspected human carcinogen.

    Science.gov (United States)

    Koerselman, W; van der Graaf, M

    1984-01-01

    The literature on carcinogenicity of acrylonitrile (an important intermediate in the chemical industry) is reviewed. The three main conclusions are: (1) Acrylonitrile has genotoxic effects in various tests in microorganisms and in mammal cells. (2) Chronic exposure to acrylonitrile causes tumours in rats. (3) Results of epidemiological studies indicate that acrylonitrile may be a human carcinogen. From this it is clear that acrylonitrile is very probably carcinogenic to humans. Therefore the authors plead for a reduction of acrylonitrile standards to the lowest practicable limit.

  9. Rodent Research-1 Validation of Rodent Hardware

    Science.gov (United States)

    Globus, Ruth; Beegle, Janet

    2013-01-01

    To achieve novel science objectives, validation of a rodent habitat on ISS will enable - In-flight analyses during long duration spaceflight- Use of genetically altered animals- Application of modern analytical techniques (e.g. genomics, proteomics, and metabolomics)

  10. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation.

    Science.gov (United States)

    Herceg, Zdenko; Lambert, Marie-Pierre; van Veldhoven, Karin; Demetriou, Christiana; Vineis, Paolo; Smith, Martyn T; Straif, Kurt; Wild, Christopher P

    2013-09-01

    Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and various fields of biomedical research. The result is a broader appreciation of epigenetic phenomena in the a etiology of common human diseases, most notably cancer. These advances also represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, are expected to generate information for establishing the 'normal' epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Recently, epigenetic events have emerged as key mechanisms in cancer development, and while our search of the Monograph Volume 100 revealed that epigenetics have played a modest role in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs so far, epigenetic data might play a pivotal role in the future. Here, we review (i) the current status of incorporation of epigenetics in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences and (v) critical technological and biological issues in assessment of epigenetic carcinogens. We also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation. Although the application of epigenetic assays in carcinogen evaluation is still in its infancy, important data are being generated and valuable scientific resources are being established that should catalyse future applications of epigenetic testing.

  11. Predicting carcinogenicity of diverse chemicals using probabilistic neural network modeling approaches

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Kunwar P., E-mail: kpsingh_52@yahoo.com [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Gupta, Shikha; Rai, Premanjali [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India)

    2013-10-15

    Robust global models capable of discriminating positive and non-positive carcinogens; and predicting carcinogenic potency of chemicals in rodents were developed. The dataset of 834 structurally diverse chemicals extracted from Carcinogenic Potency Database (CPDB) was used which contained 466 positive and 368 non-positive carcinogens. Twelve non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals and nonlinearity in the data were evaluated using Tanimoto similarity index and Brock–Dechert–Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) models were constructed for classification and function optimization problems using the carcinogenicity end point in rat. Validation of the models was performed using the internal and external procedures employing a wide series of statistical checks. PNN constructed using five descriptors rendered classification accuracy of 92.09% in complete rat data. The PNN model rendered classification accuracies of 91.77%, 80.70% and 92.08% in mouse, hamster and pesticide data, respectively. The GRNN constructed with nine descriptors yielded correlation coefficient of 0.896 between the measured and predicted carcinogenic potency with mean squared error (MSE) of 0.44 in complete rat data. The rat carcinogenicity model (GRNN) applied to the mouse and hamster data yielded correlation coefficient and MSE of 0.758, 0.71 and 0.760, 0.46, respectively. The results suggest for wide applicability of the inter-species models in predicting carcinogenic potency of chemicals. Both the PNN and GRNN (inter-species) models constructed here can be useful tools in predicting the carcinogenicity of new chemicals for regulatory purposes. - Graphical abstract: Figure (a) shows classification accuracies (positive and non-positive carcinogens) in rat, mouse, hamster, and pesticide data yielded by optimal PNN model. Figure (b) shows generalization and predictive

  12. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Kakehashi, Anna; Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)

    2013-10-28

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P{sub 450} inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  13. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Directory of Open Access Journals (Sweden)

    Hideki Wanibuchi

    2013-10-01

    Full Text Available This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  14. An industry perspective on the utility of short-term carcinogenicity testing in transgenic mice in pharmaceutical development.

    Science.gov (United States)

    Storer, Richard D; Sistare, Frank D; Reddy, M Vijayaraj; DeGeorge, Joseph J

    2010-01-01

    International guidelines allow for use of a short-term cancer bioassay (twenty-six weeks) in transgenic mice as a substitute for one of the two required long-term rodent bioassays in the preclinical safety evaluation of pharmaceuticals. The two models that have gained the widest acceptance by sponsors and regulatory authorities are the CB6F1-RasH2 mouse hemizygous for a human H-ras transgene and the B6.129N5-Trp53 mouse heterozygous for a p53 null allele. The p53(+/-) model is of particular value for compounds with residual concern that genotoxic activity may contribute to tumorigenesis. The rasH2 model is an appropriate alternative without regard to evidence of genotoxic potential. Since results from a short-term bioassay can be obtained relatively early in drug development, there is the potential for more timely assessment of cancer risk for individuals in long-term clinical trials. Use of these models in preclinical safety evaluation also significantly reduces animal use, time, and manpower. Preliminary findings indicate that prediction of two-year rat bioassay outcomes based on data from chronic rat toxicity studies, together with early assessment of carcinogenic potential in short-term transgenic models, may have the potential to increase the timeliness and efficiency of strategies for the identification of human carcinogenic hazards.

  15. Effects of chemical carcinogens of hemopoiesis, immunopoiesis and viral oncogenesis. Technical progress report, December 1, 1977--September 30, 1978. [Mechanisms of potentiation of viral leukemogenesis by MMS, benzopyrene, and DMBA

    Energy Technology Data Exchange (ETDEWEB)

    OKunewick, J.P.; Raikow, R.B.; Meredith, R.F.

    1978-10-01

    During the past year we have concentrated on defining the circumstances under which methyl methanesulfonate (MMS), benzo(a) pyrene (BP), and 7,12-dimethylbenz(a)anthracene (DMBA) interact with Friend virus (FLV) to produce leukemia. The optimum scheduling for each and also the effective dose levels of the chemicals have been partially determined. There are at least three critical factors which govern whether or not a leukemogenic interaction can be shown between the chemical agents and the virus. These are chemical dose, virus dose, and their relative time of administration. The most critical of these is virus dose. The optimum virus dose is that which results in between 25 and 40% incidence of leukemia within 40 days after virus infection when virus is given alone. The chemical carcinogens have a lower dose threshold, below which no significant potentiating effect can be observed. The only upper limit would appear to be acute drug toxicity. The third element, timing, is equally critical and varies according to the chemical. This variation may reflect different mechanisms of action by the chemical agents and/or different pharmacology. Data on the effects of MMS, BP, and DMBA on the immune system have indicated that the viral enhancement is probably not dependent on this function. Further enhancement of the potentiation of viral leukemogenesis was observed using benzo(a)pyrene and caffeine, indicating that the inhibition by caffeine of DNA repair may be an important factor in virus potentiation. (ERB)

  16. [Fiber as a carcinogenic agent].

    Science.gov (United States)

    Pott, F

    1987-04-01

    According to the findings that long, thin, and durable fibres have a high carcinogenic potency after intrapleural and intraperitoneal administration, the elongated shape of a particle represents a carcinogenic agent; this physical phenomenon is a special cause of cancer. It induces a biological process which can lead to cancer by several as yet unknown steps. However, the properties of the material the fibres are made of determine the carcinogenic potency of a fibre in a secondary way although they do not seem to be responsible for the true carcinogenic agent. For example, these properties determine the degree of solubility and flexibility. The persistence of fibres in the tissue is a very important property with regard to their carcinogenic effect because the formation of a tumour takes many years or some decades. It can be assumed that a fibre has to remain by the bronchial or serosa tissue until the induction of tumour cells occurs. If this hypothesis is correct, there could be a "durability threshold value" for fibres whose length and diameter would otherwise indicate a high carcinogenic potency. There are indications that other fibre properties apart from length, diameter and durability are important for tumour induction, however, at present, they cannot be included in a definition of carcinogenic fibres. It is proposed to classify all natural and man-made mineral fibres with an aspect ratio of greater than 5:1 as carcinogenic when they are longer than 3 microns, thinner than 1 micron (or can split into such fine fibres) and when they can persist in the tissue for more than 3 years.

  17. Rodent Models for Metabolic Syndrome Research

    Directory of Open Access Journals (Sweden)

    Sunil K. Panchal

    2011-01-01

    Full Text Available Rodents are widely used to mimic human diseases to improve understanding of the causes and progression of disease symptoms and to test potential therapeutic interventions. Chronic diseases such as obesity, diabetes and hypertension, together known as the metabolic syndrome, are causing increasing morbidity and mortality. To control these diseases, research in rodent models that closely mimic the changes in humans is essential. This review will examine the adequacy of the many rodent models of metabolic syndrome to mimic the causes and progression of the disease in humans. The primary criterion will be whether a rodent model initiates all of the signs, especially obesity, diabetes, hypertension and dysfunction of the heart, blood vessels, liver and kidney, primarily by diet since these are the diet-induced signs in humans with metabolic syndrome. We conclude that the model that comes closest to fulfilling this criterion is the high carbohydrate, high fat-fed male rodent.

  18. Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential.

    Science.gov (United States)

    Walker, Claire-Dominique; Bath, Kevin G; Joels, Marian; Korosi, Aniko; Larauche, Muriel; Lucassen, Paul J; Morris, Margaret J; Raineki, Charlis; Roth, Tania L; Sullivan, Regina M; Taché, Yvette; Baram, Tallie Z

    2017-07-12

    The immediate and long-term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional, and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here, we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current

  19. Biodegradation of the metallic carcinogen hexavalent chromium Cr(VI) by an indigenously isolated bacterial strain

    National Research Council Canada - National Science Library

    Das, Alok Prasad; Mishra, Susmita

    2010-01-01

    Hexavalent chromium [Cr(VI)], a potential mutagen and carcinogen, is regularly introduced into the environment through diverse anthropogenic activities, including electroplating, leather tanning, and pigment manufacturing...

  20. Vinyl acetate monomer (VAM) genotoxicity profile: relevance for carcinogenicity.

    Science.gov (United States)

    Albertini, Richard J

    2013-09-01

    Vinyl acetate monomer (VAM) is a site-of-contact carcinogen in rodents. It is also DNA reactive and mutagenic, but only after its carboxylesterase mediated conversion to acetaldehyde (AA), a metabolic reaction that also produces acetic acid and protons. As VAM's mutagenic metabolite, AA is normally produced endogenously; detoxification by aldehyde dehydrogenase (ALDH) is required to maintain intra-cellular AA homeostasis. This review examines VAM's overall genotoxicity, which is due to and limited by AA, and the processes leading to mutation induction. VAM and AA have both been universally negative in mutation studies in bacteria but both have tested positive in several in vitro studies in higher organisms that usually employed high concentrations of test agents. Recently however, in vitro studies evaluating submillimolar concentrations of VAM or AA have shown threshold dose-responses for mutagenicity in human cultured cells. Neither VAM nor AA induced systemic mutagenicity in in vivo studies in metabolically competent mice when tested at non-lethal doses while treatments of animals deficient in aldehyde dehydrogenase (Aldh in animals) did induce both gene and chromosome level mutations. The results of several studies have reinforced the critical role for aldehyde dehydrogenase 2 (ALDH2 in humans) in limiting AA's (and therefore VAM's) mutagenicity. The overall aim of this review of VAM's mutagenic potential through its AA metabolite is to propose a mode of action (MOA) for VAM's site-of-contact carcinogenesis that incorporates the overall process of mutation induction that includes both background mutations due to endogenous AA and those resulting from exogenous exposures.

  1. RADON AND CARCINOGENIC RISK IN MOSCOW

    Directory of Open Access Journals (Sweden)

    S. M. Golovanev

    2015-01-01

    Full Text Available Objective: comparative evaluation of carcinogenic risk inMoscowfrom radon in indoor and atmospheric pollutants.Materials and methods: the lung cancer incidence in Moscow; radiation-hygienic passport of the territory; .U.S. EPA estimated average age at all and radon induced deaths, years of life lost; Report of UNSCEAR 2006 and WHO handbook on indoor radon, 2009. Trend analysis of incidence; evaluation of the excess relative risk; assessment of ratio radon-induced population risk and published values оf total population carcinogenic risk from chemical carcinogens.Results: it is shown that the 304 cases of lung cancer per year (1. 85 10-3 on average from 2006 to 2011 (21280diseases for 70 years in addition to background level induced by radon; the differences in average trends of all lungcancer incidence in the districts can exceed 25%.Conclusion. The potential of risk reduction by measures of mitigation radon concentration exceeds 5 times the cost efficiency to reduce emissions from vehicles and can reduce cancer incidence, on average 236 cases per year; population risk 16520 cases over 70 years or save not less than 2832 person-years of life per year. The annual effect of reducing losses from not-survival of 12 years as a result of radon-induced lung cancer deaths exceeds 14160000 dollars. The evaluating of the carcinogenic risk from radon in accordance with the definition of population risk increases the predictive evaluation of the effectiveness of preventive measures more than twice.

  2. Carcinogenicity of hair dye components.

    Science.gov (United States)

    Van Duuren, B L

    1980-03-01

    The available animal carcinogenicity data on hair dye components was reviewed. From this review it became clear that certain hair dye components, some of which are still in hair dye formulations now on the market, are animal carcinogens. The compounds of concern that are still in use are: 3-amino-4-methoxyaniline, 2-nitro-4-aminoaniline and 3-nitro-4-hydroxyaniline. Certain azo dyes formerly used, and related compounds still in use, contain the benzidine moiety. Two of these compounds, Direct Blue 6 and Direct Black 38, have been shown to be metabolized in animals to the human carcinogen benzidine. Furthermore, skin absorption studies carried out with radiolabeled hair dye components applied to animal or human skin have conclusively shown that these compounds are systemically absorbed and excreted. Known cocarcinogens such as catechol and pyrogallol, which enhance benzo(a)pyrene carcinogenicity on mouse skin, are used as hair dye components. It is not known whether such compounds will enhance the carcinogenicity of substituted aniline hair dye chemicals. The available epidemiologic data are not sufficient to link hair dye use with an increased incidence in human cancer.

  3. Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile.

    Science.gov (United States)

    Léonard, A; Gerber, G B; Stecca, C; Rueff, J; Borba, H; Farmer, P B; Sram, R J; Czeizel, A E; Kalina, I

    1999-05-01

    Acrylonitrile (AN) is an important intermediary for the synthesis of a variety of organic products, such as artificial fibres, household articles and resins. Although acute effects are the primary concern for an exposure to AN, potential genotoxic, carcinogenic and teratogenic risks of AN have to be taken seriously in view of the large number of workers employed in such industries and the world-wide population using products containing and possibly liberating AN. An understanding of the effect of acrylonitrile must be based on a characterization of its metabolism as well as of the resulting products and their genotoxic properties. Tests for mutagenicity in bacteria have in general been positive, those in plants and on unscheduled DNA synthesis doubtful, and those on chromosome aberrations in vivo negative. Wherever positive results had been obtained, metabolic activation of AN appeared to be a prerequisite. The extent to which such mutagenic effects are significant in man depends, however, also on the conditions of exposure. It appears from the limited data that the ultimate mutagenic factor(s), such as 2-cyanoethylene oxide, may have little opportunity to act under conditions where people are exposed because it is formed only in small amounts and is rapidly degraded. The carcinogenic action of AN has been evaluated by various agencies and ranged from 'reasonably be anticipated to be a human carcinogen' to 'cannot be excluded', the most recent evaluation being 'possibly carcinogenic to humans'. Animal data that confirm the carcinogenic potential of AN have certain limitations with respect to the choice of species, type of tumors and length of follow up. Epidemiological studies which sometimes, but not always, yielded positive results, encounter the usual difficulties of confounding factors in chemical industries. Exposure of workers to AN should continue to be carefully monitored, but AN would not have to be considered a cancer risk to the population provided

  4. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    Directory of Open Access Journals (Sweden)

    Bryan L. Stegelmeier

    2016-11-01

    Full Text Available Dehydropyrrolizidine alkaloid (DHPA-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health.

  5. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    Science.gov (United States)

    Stegelmeier, Bryan L.; Colegate, Steven M.; Brown, Ammon W.

    2016-01-01

    Dehydropyrrolizidine alkaloid (DHPA)-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health. PMID:27916846

  6. Short-term effects on antioxidant enzymes and long-term genotoxic and carcinogenic potential of CuO nanoparticles compared to bulk CuO and ionic copper in mussels Mytilus galloprovincialis.

    Science.gov (United States)

    Ruiz, Pamela; Katsumiti, Alberto; Nieto, Jose A; Bori, Jaume; Jimeno-Romero, Alba; Reip, Paul; Arostegui, Inmaculada; Orbea, Amaia; Cajaraville, Miren P

    2015-10-01

    The aim of this work was to study short-term effects on antioxidant enzyme activities and long-term genotoxic and carcinogenic potential of CuO nanoparticles (NPs) in comparison to bulk CuO and ionic copper in mussels Mytilus galloprovincialis after 21 days exposure to 10 μg Cu L(-1). Then, mussels were kept for up to 122 days in clean water. Cu accumulation depended on the form of the metal and on the exposure time. CuO NPs were localized in lysosomes of digestive cells, as confirmed by TEM and X ray microanalysis. CuO NPs, bulk CuO and ionic copper produced different effects on antioxidant enzyme activities in digestive glands, overall increasing antioxidant activities. CuO NPs significantly induced catalase and superoxide dismutase activities. Fewer effects were observed in gills. Micronuclei frequency increased significantly in mussels exposed to CuO NPs and one organism treated with CuO NPs showed disseminated neoplasia. However, transcription levels of cancer-related genes did not vary significantly. Thus, short-term exposure to CuO NPs provoked oxidative stress and genotoxicity, but further studies are needed to determine whether these early events can lead to cancer development in mussels.

  7. Therapeutic potential of RQ-00311651, a novel T-type Ca2+ channel blocker, in distinct rodent models for neuropathic and visceral pain.

    Science.gov (United States)

    Sekiguchi, Fumiko; Kawara, Yuma; Tsubota, Maho; Kawakami, Eri; Ozaki, Tomoka; Kawaishi, Yudai; Tomita, Shiori; Kanaoka, Daiki; Yoshida, Shigeru; Ohkubo, Tsuyako; Kawabata, Atsufumi

    2016-08-01

    T-type Ca channels (T channels), particularly Cav3.2 among the 3 isoforms, play a role in neuropathic and visceral pain. We thus characterized the effects of RQ-00311651 (RQ), a novel T-channel blocker, in HEK293 cells transfected with human Cav3.1 or Cav3.2 by electrophysiological and fluorescent Ca signaling assays, and also evaluated the antiallodynic/antihyperalgesic activity of RQ in somatic, visceral, and neuropathic pain models in rodents. RQ-00311651 strongly suppressed T currents when tested at holding potentials of -65 ∼ -60 mV, but not -80 mV, in the Cav3.1- or Cav3.2-expressing cells. RQ-00311651 also inhibited high K-induced Ca signaling in those cells. In mice, RQ, administered intraperitoneally (i.p.) at 5 to 20 mg/kg or orally at 20 to 40 mg/kg, significantly suppressed the somatic hyperalgesia and visceral pain-like nociceptive behavior/referred hyperalgesia caused by intraplantar and intracolonic administration of NaHS or Na2S, H2S donors, respectively, which involve the enhanced activity of Cav3.2 channels. RQ-00311651, given i.p. at 5 to 20 mg/kg, exhibited antiallodynic or antihyperalgesic activity in rats with spinal nerve injury-induced neuropathy or in rats and mice with paclitaxel-induced neuropathy. Oral and i.p. RQ at 10 to 20 mg/kg also suppressed the visceral nociceptive behavior and/or referred hyperalgesia accompanying cerulein-induced acute pancreatitis and cyclophosphamide-induced cystitis in mice. The analgesic and antihyperalgesic/antiallodynic doses of oral and i.p. RQ did not significantly affect the locomotor activity and motor coordination. Together, RQ is considered a state-dependent blocker of Cav3.1/Cav3.2 T channels and may serve as an orally available analgesic for treatment of neuropathic and inflammatory pain including distinct visceral pain with minimum central side effects.

  8. A cross-sectional study on the potential transmission of the carcinogenic liver fluke Opisthorchis viverrini and other fishborne zoonotic trematodes by aquaculture fish.

    Science.gov (United States)

    Pitaksakulrat, Opal; Sithithaworn, Paiboon; Laoprom, Nonglak; Laha, Thewarach; Petney, Trevor N; Andrews, Ross H

    2013-01-01

    Throughout Southeast Asia and China, eating raw and or partially cooked cyprinid fish causes liver (hepatobiliary) disease and cancer (cholangiocarcinoma) due to fishborne zoonotic trematodes (FZT), in particular Clonorchis sinensis and Opisthorchis viverrini. The primary source of transmission is by native fish, but aquaculture fish are also reported to have high infective potential. Here, a cross-sectional survey of FZT in fish farms was conducted in an endemic area in Khon Kaen Province, Thailand. By using conventional and polymerase chain reaction (PCR) methods, we detected O. viverrini and FZT metacercariae (Centrocestus formosanus and Haplorchis taichui) in two popular fish species, Barbonymus gonionotus (silver barb) and Cirrhinus mrigala (mrigal), from aquaculture farms. Both species were infected in five of six farms examined by PCR but not by conventional methods, yet the prevalence of FZT metacercariae in aquaculture fish was high (46.9%). In addition to O. viverrini (17.1%), the native fish Cyclocheilichthys armatus and Hampala dispar had a prevalence of FZT of 81.4%, which included 5.7% for C. formosanus and 17.1% for H. taichui by conventional method. To our knowledge, this is the first discovery of O. viverrini in aquaculture fish in Thailand. More comprehensive studies are required to determine if human-induced disease transmission coupled with natural transmission cycle occurs throughout the aquaculture industry in the region. This has significant impact on food quality and safety, and provides the basis for the development of an effective strategy for the prevention and control of foodborne diseases.

  9. In vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus DNA-carrying C3H/10T(1/2) cell line.

    Science.gov (United States)

    Kowalski, L A; Laitinen, A M; Mortazavi-Asl, B; Wee, R K; Erb, H E; Assi, K P; Madden, Z

    2000-01-01

    A new in vitro test for predicting rodent carcinogenicity is evaluated against a testing database of 64 chemicals including both genotoxic and nongenotoxic carcinogens and carcinogens that normally require addition of an S-9 microsomal fraction for detection in the bacterial mutagenicity assay. The assay uses focus formation in a stable, bovine papillomavirus type 1 (BPV-1) DNA carrying C3H/10T(1/2) mouse embryo fibroblast cell line (T1) that does not require transfection, infection with virus, isolation of primary cells from animals, or addition of a microsomal fraction. Of a total database of 64 compounds, 92% of the carcinogens, promoters, or noncarcinogens were correctly predicted. Based on previously reported results, the test of bacterial mutagenicity would have correctly predicted 58% of carcinogens, promoters or noncarcinogens and the Syrian hamster embryo test would have correctly predicted 87% of carcinogens, promoters, or noncarcinogens of this database. Of carcinogens that normally require addition of an S-9 fraction, T1 cells correctly predicted rodent carcinogenicity of polyaromatic hydrocarbons, aflatoxins, azo-compounds, nitrosamines, and hydrazine without the addition of an S-9 fraction. Of nongenotoxic carcinogens, T1 cells correctly predicted diethylstilbestroel, diethylhexylphthalate, acetamides, alkyl halides, ethyl carbamate, and phorbol ester tumour promoters.

  10. Rodents: food or pests in Neolithic Orkney.

    Science.gov (United States)

    Romaniuk, Andrzej A; Shepherd, Alexandra N; Clarke, David V; Sheridan, Alison J; Fraser, Sheena; Bartosiewicz, László; Herman, Jeremy S

    2016-10-01

    Rodents have important effects on contemporary human societies, sometimes providing a source of food but more often as agricultural pests, or as vectors and reservoirs of disease. Skeletal remains of rodents are commonly found in archaeological assemblages from around the world, highlighting their potential importance to ancient human populations. However, there are few studies of the interactions between people and rodents at such sites and most of these are confined to locations where rodents have formed a part of the recent diet. Here we compare the accumulation pattern of rodent remains from four locations within and adjacent to the renowned Neolithic site of Skara Brae, Orkney, showing that those within the settlement itself were the result of deliberate human activity. The accumulation and nature of burnt bones, incorporated over an extended period within deposits of household waste, indicate that rodents were used as a nutritional resource and may have been the subject of early pest control. We, therefore, provide the first evidence for the exploitation or control of rodents by the Neolithic inhabitants of Europe.

  11. AGE-RELATED DIFFERENCES IN SUSCEPTIBILITY TO CARCINOGENESIS II, APPROACHES FOR APPLICATION AND UNCERTAINTY ANALYSES FOR INDIVIDUAL GENETICALLY ACTING CARCINOGENS

    Science.gov (United States)

    An earlier paper (Hattis et al., 2003) developed a quantitative likelihood-based statistical analysis of the differences in apparent sensitivity of rodents to mutagenic carcinogens across three life stages (fetal, birth-weaning, and weaning-60 days) relative to exposures in adult...

  12. Carcinogenicity of insulin analogues

    NARCIS (Netherlands)

    Braak, Sebastiaan Johannes ter

    2015-01-01

    There is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin glargine (LANTUS) was the only commercial insulin analogue with an increased mitogenic potential. In the huma

  13. RODENT LEYDIG CELL TUMORIGENESIS: A REVIEW OF THE PHYSIOLOGY, PATHOLOGY, MECHANISMS, AND RELEVANCE TO HUMANS

    Science.gov (United States)

    Leydig cells (LCs) are the cells of the testis that have as their primary function the production of testosterone. LCs are a common target of compounds tested in rodent carcinogenicity bioassays. The number of reviews on Leydig cell tumors (LCTs) has increased in recent years bec...

  14. Zoonoses of rabbits and rodents.

    Science.gov (United States)

    Hill, William Allen; Brown, Julie Paige

    2011-09-01

    Millions of households in the US own rabbits or rodents, including hamsters, guinea pigs, and gerbils. Activities such as hunting and camping also involve human interactions with wild rabbits and rodents. In many environments, feral rabbits and rodents live in close proximity to humans, domesticated animals, and other wildlife. Education of rodent and rabbit owners and individuals with occupational or recreational exposures to these species is paramount to reduce the prevalence of zoonoses associated with rabbit and rodent exposure.

  15. Studies in vitro to discern the structural requirements for carcinogenicity in analogues of the carcinogen 4-dimethylaminoazobenzene (butter yellow).

    Science.gov (United States)

    Ashby, J; Styles, J A; Paton, D

    1980-01-01

    4-Dimethylaminoazobenzene (butter yellow, DAB), is the parent member of a large family of 'azo-carcinogens'. Experiments have been conducted in vitro to determine the key structural requirements for carcinogenic activity in this chemical class, and it is suggested, based on the activity observed for 4-cyano-N,N-dimethylaniline, that the 4-phenylazo group of DAB is not an essential structural feature per se. The N-oxide derivative of DAB has been evaluated in vitro and the positive response observed related to its metabolic activation. It is concluded that cyclic amines, such as pyrrolidine, can replace the N-dimethyl group of DAB with a retention of biological activity. The confusion that exists in the literature concerning the chemical identity and carcinogenic status of 2-dimethylaminobenzo[c]cinnoline has been investigated, and it is concluded that it is a potential animal carcinogen. This observation also indicates that the phenylazo group of DAB can be incorporated within an aromatic ring system with a retention of biological activity. As observed earlier with a mixture of azobenzene and DAB, azobenzene also potentiates the cell transforming properties of the above cinnoline derivative in vitro. Two charts are presented. The first attempts to integrate DAB within a much larger family of carcinogens, and the second illustrates the usefulness of structure-activity studies in general.

  16. Cell-mediated mutagenesis and cell transformation of mammalian cells by chemical carcinogens. [Rats, hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Huberman, E.; Langenbach, R.

    1977-01-01

    We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro.

  17. Chronic toxicity and carcinogenicity study of erythritol in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bos-Kuijpers, M.H.M.; Til, H.P.; Bär, A.

    1996-01-01

    The potential toxicity and carcinogenicity of erythritol, a low-calorie sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Groups of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythritol, or 10% mannitol, for a period of 104-107 weeks. To each of these main groups, two

  18. The largest fossil rodent

    Science.gov (United States)

    Rinderknecht, Andrés; Blanco, R. Ernesto

    2008-01-01

    The discovery of an exceptionally well-preserved skull permits the description of the new South American fossil species of the rodent, Josephoartigasia monesi sp. nov. (family: Dinomyidae; Rodentia: Hystricognathi: Caviomorpha). This species with estimated body mass of nearly 1000 kg is the largest yet recorded. The skull sheds new light on the anatomy of the extinct giant rodents of the Dinomyidae, which are known mostly from isolated teeth and incomplete mandible remains. The fossil derives from San José Formation, Uruguay, usually assigned to the Pliocene–Pleistocene (4–2 Myr ago), and the proposed palaeoenvironment where this rodent lived was characterized as an estuarine or deltaic system with forest communities. PMID:18198140

  19. Opportunities for an alternative integrating testing strategy for carcinogen hazard assessment?

    Science.gov (United States)

    Doktorova, Tatyana Y; Pauwels, Marleen; Vinken, Mathieu; Vanhaecke, Tamara; Rogiers, Vera

    2012-02-01

    The 2-year rodent carcinogenicity bioassay evolved more than 40 years ago, and although it is complex, long lasting, expensive, and animal consuming, it is still the only generally accepted test for assessing the carcinogenicity of chemicals. Over time, different alternative approaches have been developed with the final goal to replace the bioassay. Unfortunately, at present, none of these strategies alone provides sufficient assurance of accurate prediction. In this review paper, we discuss the major advantages and pitfalls of the existing alternative methodologies to the carcinogenicity bioassay. Finally, based on the available scientific data in the public domain, we propose what we would like to call a "feasible integrated testing strategy" which incorporates some promising alternatives, providing at the same time information on the mechanism of action and the toxic nature of the compounds tested. It is, however, clear that the adoption of whatever "new" testing scheme should be considered with caution and its effectiveness should be experimentally demonstrated in advance by addressing a reasonable number of chemical carcinogens and non-carcinogens from a variety of structural and functional classes.

  20. Helminths in rodents from Wet Markets in Thailand

    Directory of Open Access Journals (Sweden)

    Ribas A.

    2016-12-01

    Full Text Available Only a few surveys have ever been carried out of the helminths of the commensal rodents found in the traditional wet markets that play such an important part of daily life in South-east Asia. The potential of rodents as reservoirs of zoonoses including helminths is of great interest since in these markets humans and rodents come into closer contact than in other environments and food may be indirectly contaminated via rodent faeces. Helminths in a total of 98 rats belonging to two species (Rattus norvegicus and Rattus exulans were surveyed in eight traditional wet markets in Udon Thani, Thailand. Thirteen species of helminths were recovered, seven of which are potentially zoo-notic, with an overall prevalence of 89.8 %. Our results show that rodents in wet markets could pose a threat to human health as potential reservoirs of zoonotic helminthiases.

  1. Uus Multiphonic Rodent

    Index Scriptorium Estoniae

    2009-01-01

    Tartus tegutsenud eksperimentaal-rock-duo Opium Flirt Eestisse jäänud liige Erki Hõbe (paarimees Ervin Trofimov tegutseb Ungaris) annab välja oma teise sooloalbumi nime all Multiphonic Rodent, heliplaadi "Astral Dance" esitluskontsert toimub 5. veebruaril Tallinnas baaris Juuksur

  2. Rodents of the Caribbean

    DEFF Research Database (Denmark)

    Fabre, Pierre-Henri; Mouatt, Julia Thidamarth Vilstrup; Raghavan, Maanasa;

    2014-01-01

    The Capromyidae (hutias) are endemic rodents of the Caribbean and represent a model of dispersal for non-flying mammals in the Greater Antilles. This family has experienced severe extinctions during the Holocene and its phylogenetic affinities with respect to other caviomorph relatives are still...

  3. Investigating the Mechanism of Action and the Identification of Breast Carcinogens by Computational Analysis of Female Rodent Carcinogens

    Science.gov (United States)

    2006-08-01

    million Center of Biomedical Research Excellence ( COBRE ) grant from the National Center for Research Resources at the National Institutes of Health...three year COBRE -funded project in Molecular Targets. My recruitment to the University of Louisville’s Brown Cancer Center and my proposed COBRE ...preparing a COBRE Molecular Targets Project with a goal to extend the computational work of Specific Aims of this project to the discovery of novel

  4. Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms.

    Science.gov (United States)

    Ge, Guang-Zhe; Xu, Tian-Rui; Chen, Ceshi

    2015-07-01

    Tobacco usage is a major risk factor in the development, progression, and outcomes for lung cancer. Of the carcinogens associated with lung cancer, tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is among the most potent ones. The oncogenic mechanisms of NNK are not entirely understood, hindering the development of effective strategies for preventing and treating smoking-associated lung cancers. Here, we introduce the NNK-induced lung cancer animal models in different species and its potential mechanisms. Finally, we summarize several chemopreventive agents developed from these animal models.

  5. The fecal viral flora of wild rodents.

    Directory of Open Access Journals (Sweden)

    Tung G Phan

    2011-09-01

    Full Text Available The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in

  6. A RASH analysis of National Toxicology Program data: Predictions for 30 compounds to be tested in rodent carcinogenesis experiments

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T.D.; Easterly, C.E. [Oak Ridge National Lab., TN (United States)

    1996-10-01

    Relative potencies for 30 compounds scheduled for carcinogenic testing in the 2-year rodent bioassays were estimated based on comparisons with a wide variety of bioassay data for benzo[a]pyrene, nicotine, cisplatin, aflatoxin B1, and cyclophosphamide. Potential for oncogenic transformation of each of the compounds was estimated from short-term bioassays. Promoting strength was assigned on the basis of comparisons of the product of relative potency and test dose with the distribution of similar products obtained for 67 common compounds in the data- base of Gold et al. A potency class for promotion was assigned on the basis of whether the potency-adjusted test dosage was > 2{sigma} below the mean, > 1{sigma} below the mean, within {+-}{sigma} of the mean, >{sigma} above the mean, or > 2{sigma} above the mean, as determined from the 67 compounds. The underlying hypothesis is that a weak test dose may have a low probability of revealing a potential carcinogen, whereas a strong dose may have a high probability of producing false-positive results. Predictions are therefore directed at the central 68% of the log-normal frequency distribution according to the assumption that {+-}{sigma} represents the ideal test dose. 22 refs., 7 tabs.

  7. A call to expand regulation to all carcinogenic fibrous minerals

    Science.gov (United States)

    Baumann, F.; Steele, I.; Ambrosi, J.; Carbone, M.

    2013-05-01

    The regulatory term "asbestos" groups only the six fibrous minerals that were commercially used among approximately 400. The carcinogenicity of these six regulated minerals has been largely demonstrated and is related to fiber structure, fiber length/diameter ratio, and bio-persistence. From a public perception, the generic term "asbestos" refers to the fibrous minerals that cause asbestosis, mesothelioma and other cancers. However, other non-regulated fibrous minerals are potentially as dangerous as the regulatory asbestos because they share similar physical and chemical properties, epidemiological studies have demonstrated their relationship with asbestos-related diseases, and both in vitro and in vivo experiments have established the toxicity of these minerals. For example, the non-regulated asbestiform winchite and richterite minerals that contaminated the vermiculite mined from Libby, Montana, (USA) were associated with mesothelioma, lung cancer and asbestosis observed among the area's residents and miners. Many other examples of non-regulated carcinogenic fibrous minerals include, but are not limited to, antigorite, arfvedsonite, balangeroite, carlosturanite, erionite, fluoro-edenite, hornblende, mordenite, palygorskite, and sepiolite. To propose a regulatory definition that would provide protection from all carcinogenic fibers, we have conducted an interdisciplinary literature review to compare the characteristics of "asbestos" and of non-regulated mineral fibers that relate to carcinogenicity. We specifically studied two non-regulated fibrous minerals that are associated with asbestos-related diseases: the serpentine antigorite and the zeolite erionite. Both examples underscore the problem of regulation based on commercial, rather than scientific principles: 1) the occurrence of fibrous antigorite in materials used to pave roads has been correlated with high mesothelioma rates in New Caledonia. Antigorite was also the cause of asbestosis in Poland, and in

  8. Carcinogenicity and other health effects of acrylonitrile with reference to occupational exposure limit.

    Science.gov (United States)

    Sakurai, H

    2000-04-01

    The occupational exposure limit for acrylonitrile (AN) has been set by many organizations on the basis of its carcinogenicity. However, recent epidemiological studies do not afford evidence supporting the hypothesis that AN is carcinogenic to humans. Review of the 18 published cohort studies revealed that, although there is not adequate evidence in humans for carcinogenicity of AN, the possibility of a causal association between high exposure to AN and lung cancer in humans cannot be excluded. It was pointed out that carcinogenic potential of AN may be weak, if any, to humans, and the current occupational exposure limit (OEL) for AN of 2 ppm was evaluated as appropriate in view of AN exposure levels reported by epidemiological studies. Based also on review of the literature on health effects other than carcinogenicity, it was concluded that the current OEL for AN is a reasonable value and there is no need for a revision at present.

  9. Lactoperoxidase-catalyzed activation of carcinogenic aromatic and heterocyclic amines.

    Science.gov (United States)

    Gorlewska-Roberts, Katarzyna M; Teitel, Candee H; Lay, Jackson O; Roberts, Dean W; Kadlubar, Fred F

    2004-12-01

    Lactoperoxidase, an enzyme secreted from the human mammary gland, plays a host defensive role through antimicrobial activity. It has been implicated in mutagenic and carcinogenic activation in the human mammary gland. The potential role of heterocyclic and aromatic amines in the etiology of breast cancer led us to examination of the lactoperoxidase-catalyzed activation of the most commonly studied arylamine carcinogens: 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), benzidine, 4-aminobiphenyl (ABP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). In vitro activation was performed with lactoperoxidase (partially purified from bovine milk or human milk) in the presence of hydrogen peroxide and calf thymus DNA. Products formed during enzymatic activation were monitored by HPLC with ultraviolet and radiometric detection. Two of these products were characterized as hydrazo and azo derivatives by means of mass spectrometry. The DNA binding level of 3H- and 14C-radiolabeled amines after peroxidase-catalyzed activation was dependent on the hydrogen peroxide concentration, and the highest levels of carcinogen binding to DNA were observed at 100 microM H2O2. Carcinogen activation and the level of binding to DNA were in the order of benzidine > ABP > IQ > MeIQx > PhIP. One of the ABP adducts was identified, and the level at which it is formed was estimated to be six adducts/10(5) nucleotides. The susceptibility of aromatic and heterocyclic amines for lactoperoxidase-catalyzed activation and the binding levels of activated products to DNA suggest a potential role of lactoperoxidase-catalyzed activation of carcinogens in the etiology of breast cancer.

  10. Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia.

    Science.gov (United States)

    Mizoguchi, Yoshito; Kato, Takahiro A; Seki, Yoshihiro; Ohgidani, Masahiro; Sagata, Noriaki; Horikawa, Hideki; Yamauchi, Yusuke; Sato-Kasai, Mina; Hayakawa, Kohei; Inoue, Ryuji; Kanba, Shigenobu; Monji, Akira

    2014-06-27

    Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca(2+) elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders.

  11. Hunting, Food Preparation, and Consumption of Rodents in Lao PDR.

    Directory of Open Access Journals (Sweden)

    Kanokwan Suwannarong

    Full Text Available A cross-sectional study was conducted in 29 villages of Khamkeuth District in Bolikhamxay Province in the Lao PDR during March to May 2013. The study aimed to determine the characteristics associated with rodent consumption and related behaviors among different ethnic groups, ages, and genders. Five-hundred-eighty-four (584 males and females from 18-50 years of age participated in this study. Half of them were Hmong (292, 50% while 152 respondents were Lao-Tai (26% or other ethnic groups (140, 24%. Most of the respondents (79.5% had farming as their main occupation. Prevalences of the studied outcomes were high: 39.9 for hunting or capturing rodents in the previous year, 77.7% for preparing rodents as food, and 86.3% for rodent consumption. Multivariable logistic regression analysis showed that likelihood of these types of rodent contact was more consistently associated with behavioral factors (gathering things from the forest and elsewhere, cultivation-related activities, and taking measures to prevent rodent-borne disease than with socio-demographic, environmental, or cultural factors. The strongest associations were observed for gathering things; these associations were consistently positive and statistically significant. Although this study did not directly assess rodent-borne zoonosis risk, we believe that study findings raise concern that such risk may be substantial in the study area and other similar areas. Further epidemiological studies on the association between rodent-borne disease infection and rodent hunting, preparation for food, and consumption are recommended. Moreover, further studies are needed on the association between these potential exposure factors (i.e., rodent hunting, preparation for food, and consumption and rodent-borne infections, especially among ethnic groups like the Hmong in Lao PDR and those in neighboring countries with similar socio-demographic, environmental, behavioral and cultural contexts.

  12. Hunting, Food Preparation, and Consumption of Rodents in Lao PDR.

    Science.gov (United States)

    Suwannarong, Kanokwan; Chapman, Robert S; Lantican, Cecile; Michaelides, Tula; Zimicki, Susan

    2015-01-01

    A cross-sectional study was conducted in 29 villages of Khamkeuth District in Bolikhamxay Province in the Lao PDR during March to May 2013. The study aimed to determine the characteristics associated with rodent consumption and related behaviors among different ethnic groups, ages, and genders. Five-hundred-eighty-four (584) males and females from 18-50 years of age participated in this study. Half of them were Hmong (292, 50%) while 152 respondents were Lao-Tai (26%) or other ethnic groups (140, 24%). Most of the respondents (79.5%) had farming as their main occupation. Prevalences of the studied outcomes were high: 39.9 for hunting or capturing rodents in the previous year, 77.7% for preparing rodents as food, and 86.3% for rodent consumption. Multivariable logistic regression analysis showed that likelihood of these types of rodent contact was more consistently associated with behavioral factors (gathering things from the forest and elsewhere, cultivation-related activities, and taking measures to prevent rodent-borne disease) than with socio-demographic, environmental, or cultural factors. The strongest associations were observed for gathering things; these associations were consistently positive and statistically significant. Although this study did not directly assess rodent-borne zoonosis risk, we believe that study findings raise concern that such risk may be substantial in the study area and other similar areas. Further epidemiological studies on the association between rodent-borne disease infection and rodent hunting, preparation for food, and consumption are recommended. Moreover, further studies are needed on the association between these potential exposure factors (i.e., rodent hunting, preparation for food, and consumption) and rodent-borne infections, especially among ethnic groups like the Hmong in Lao PDR and those in neighboring countries with similar socio-demographic, environmental, behavioral and cultural contexts.

  13. Moving forward in carcinogenicity assessment: Report of an EURL ECVAM/ESTIV workshop.

    Science.gov (United States)

    Corvi, Raffaella; Madia, Federica; Guyton, Kathryn Z; Kasper, Peter; Rudel, Ruthann; Colacci, Annamaria; Kleinjans, Jos; Jennings, Paul

    2017-09-11

    There is an increased need to develop novel alternative approaches to the two-year rodent bioassay for the carcinogenicity assessment of substances where the rodent bioassay is still a basic requirement, as well as for those substances where animal use is banned or limited or where information gaps are identified within legislation. The current progress in this area was addressed in a EURL ECVAM- ESTIV workshop held in October 2016, in Juan les Pins. A number of initiatives were presented and discussed, including data-driven, technology-driven and pathway-driven approaches. Despite a seemingly diverse range of strategic developments, commonalities are emerging. For example, providing insight into carcinogenicity mechanisms is becoming an increasingly appreciated aspect of hazard assessment and is suggested to be the best strategy to drive new developments. Thus, now more than ever, there is a need to combine and focus efforts towards the integration of available information between sectors. Such cross-sectorial harmonisation will aid in building confidence in new approach methods leading to increased implementation and thus a decreased necessity for the two-year rodent bioassay. Copyright © 2017. Published by Elsevier Ltd.

  14. A glimpse on the pattern of rodent diversification

    DEFF Research Database (Denmark)

    Fabre, Pierre-Henri Fréderic; Hautier, Lionel; Dimitrov, Dimitar Stefanov;

    2012-01-01

    a rodent maximum likelihood phylogeny inferred from a molecular supermatrix. It is based on 11 mitochondrial and nuclear genes that covers 1,265 species, i.e., respectively 56% and 81% of the known specific and generic rodent diversity. The inferred topology recovered all Rodentia clades proposed by recent...... in diversification rates within the major clades: two in Castorimorpha, three in Ctenohystrica, 6 within the squirrel-related clade and 24 in the Myomorpha clade. The majority of these shifts occurred within the most recent familial rodent radiations: the Cricetidae and Muridae clades. Using the topological...... imbalances and the time line we discuss the potential role of different diversification factors that might have shaped the rodents radiation. CONCLUSIONS:The present glimpse on the diversification pattern of rodents can be used for further comparative meta-analyses. Muroid lineages have a greater degree...

  15. Human exposure to dioxins through the diet in Catalonia, Spain: carcinogenic and non-carcinogenic risk.

    Science.gov (United States)

    Llobet, Juan M; Domingo, Jose L; Bocio, Ana; Casas, Conrad; Teixidó, Angel; Müller, Lutz

    2003-03-01

    The main objectives of this study were to estimate the dietary intake of dioxins by the population of Catalonia, Spain, to determine which food groups showed the greatest contribution to this intake, and to assess the health risks potentially associated with the dietary dioxin intake. From June to August 2000, food samples were randomly acquired in seven cities of Catalonia. Dioxin concentrations were determined in 108 samples belonging to the following groups: vegetables, fruits, pulses, cereals, fish and shellfish, meats and meat products, eggs, milk and dairy products, and oils and fats. Estimates of average daily food consumption were obtained from recent studies. Total dietary intake of dioxins for the general population of Catalonia was estimated to be 95.4 pg WHO-TEQ/day (78.4 pg I-TEQ/day), with fish and shellfish (31%), diary products (25%), cereals (14%) and meat (13%) showing the greatest percentages of contribution to dioxin intake. The contribution of all the rest of food groups to the total dietary intake was under 20%. The non-carcinogenic risk index of dioxin intake through the diet was in the range 0.34-1.36, while the carcinogenic risk level was 1,360 excess cancer over a lifetime of 70 years. Our results corroborate the decreasing tendency in dietary intake of dioxins found in recent studies (2000-2001) from various countries.

  16. Strategies of reducing the carcinogenic risk of cytostatic agents on the basis of bioassay evaluation.

    Science.gov (United States)

    Berger, M R

    1991-01-01

    This article described strategies that can be used to reduce the carcinogenic risk of cytostatic chemotherapy and summarizes our recent experimental results. Reduction of neoplasms caused by the carcinogenic potency inherent in cytostatic agents can be obtained. (A) by chemical modifications such as: (1) exchanging a chlorine atom in N, N'-bis-(2-chloroethyl)-N-nitrosourea (BCNU) in the chloroethyl group at N'-position for a hydroxyl group to form the less carcinogenic analog N-(2-chloroethyl)-N'-(2-hydroxyethyl)-N-nitrosourea (HECNU); (2) linking chlorambucil to the steroid prednisolone to obtain a conjugate (prednimustine) with distinctly lower carcinogenic potential than chlorambucil; (3) progressive ring halogenation of phenyl-triazenes to generate agents with decreased long-term toxic risk; (B) by replacing cyclophosphamide within the carcinogenic drug combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) by vincristine to form the combination VMF which has no detectable carcinogenic potential; (C) by coadministration of cyclophosphamide and mesna to achieve a dose-related reduction of cyclophosphamide-induced urinary bladder carcinomas; (D) by administration of dinaline, a compound which reduces the spontaneous incidence of malignant tumors in rats. These examples demonstrate that the carcinogenic risk of single agents and drug combinations used for antineoplastic chemotherapy has successfully been reduced, as assessed in long-term bioassays. Such strategies should be considered in the treatment of patients with long life expectancy following cytotoxic chemotherapy.

  17. Rodent models of sleep apnea.

    Science.gov (United States)

    Davis, Eric M; O'Donnell, Christopher P

    2013-09-15

    Rodent models of sleep apnea have long been used to provide novel insight into the generation and predisposition to apneas as well as to characterize the impact of sleep apnea on cardiovascular, metabolic, and psychological health in humans. Given the significant body of work utilizing rodent models in the field of sleep apnea, the aims of this review are three-fold: first, to review the use of rodents as natural models of sleep apnea; second, to provide an overview of the experimental interventions employed in rodents to simulate sleep apnea; third, to discuss the refinement of rodent models to further our understanding of breathing abnormalities that occur during sleep. Given mounting evidence that sleep apnea impairs cognitive function, reduces quality of life, and exacerbates the course of multiple chronic diseases, rodent models will remain a high priority as a tool to interrogate both the pathophysiology and sequelae of breathing related abnormalities during sleep and to improve approaches to diagnosis and therapy.

  18. Geomagnetic field detection in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Olcese, J.; Reuss, S.; Semm, P.

    1988-01-01

    In addition to behavioral evidence for the detection of earth-strength magnetic fields (MF) by rodents, recent investigations have revealed that electrophysiological and biochemical responses to MF occur in the pineal organ and retina of rodents. In addition, ferrimagnetic deposits have been identified in the ethmoidal regions of the rodent skull. These findings point to a new sensory phenomenon, which interfaces with many fields of biology, including neuroscience, psychophysics, behavioral ecology, chronobiology and sensory physiology.

  19. Applying tobacco carcinogen and toxicant biomarkers in product regulation and cancer prevention.

    Science.gov (United States)

    Hecht, Stephen S; Yuan, Jian-Min; Hatsukami, Dorothy

    2010-06-21

    Tobacco carcinogen and toxicant biomarkers are metabolites or protein or DNA adducts of specific compounds in tobacco products. Highly reliable analytical methods, based mainly on mass spectrometry, have been developed and applied in large studies of many of these biomarkers. A panel of tobacco carcinogen and toxicant biomarkers is suggested here, and typical values for smokers and nonsmokers are summarized. This panel of biomarkers has potential applications in the new and challenging area of tobacco product regulation and in the development of rational approaches to cancer prevention by establishing carcinogen and toxicant uptake and excretion in people exposed to tobacco products.

  20. Mineral fibre persistence and carcinogenicity.

    Science.gov (United States)

    McDonald, J C

    1998-10-01

    Epidemiological research during the past 40 years has demonstrated with increasing clarity that amphibole asbestos fibres--crocidolite, amosite and tremolite--are more carcinogenic than chrysotile. A smaller number of well-controlled studies using lung burden analyses, while adding to the specificity of this conclusion, have shown that amphibole fibres also differ from chrysotile in being far more durable and biopersistent in lung tissue. Analyses of mesothelioma and lung cancer in a large cohort of Canadian chrysotile miners and millers have recently shown that the low-level presence of fibrous tremolite in these mines, rather than the chrysotile, may well be responsible. The high risk of lung cancer, but not of mesothelioma, in the chrysotile textile industry remains anomalous and cannot be explained in this way. These various findings are directly relevant to the choice of the experimental methods which should be used for screening man-made fibres for industrial use. Although it is clear that biopersistence is a major determinant of cancer risk in animals, and perhaps also in man, other factors affecting the biological activity of mineral fibres may also be important.

  1. Genotoxic effects in wild rodents (Rattus rattus and Mus musculus) in an open coal mining area.

    Science.gov (United States)

    León, Grethel; Pérez, Lyda Espitia; Linares, Juan Carlos; Hartmann, Andreas; Quintana, Milton

    2007-06-15

    Coal is a mixture of a variety of compounds containing mutagenic and carcinogenic polycyclic aromatic hydrocarbons. Exposure to coal is considered as an important non-cellular and cellular source of reactive oxygen species that can induce DNA damage. In addition, spontaneous combustion can occur in coal mining areas, further releasing compounds with detrimental effects on the environment. In this study the comet assay was used to investigate potential genotoxic effects of coal mining activities in peripheral blood cells of the wild rodents Rattus rattus and Mus musculus. The study was conducted in a coal mining area of the Municipio de Puerto Libertador, South West of the Departamento de Cordoba, Colombia. Animals from two areas in the coal mining zone and a control area located in the Municipio de Lorica were investigated. The results showed evidence that exposure to coal results in elevated primary DNA lesions in blood cells of rodents. Three different parameters for DNA damage were assessed, namely, DNA damage index, migration length and percentage damaged cells. All parameters showed statistically significantly higher values in mice and rats from the coal mining area in comparison to the animals from the control area. The parameter "DNA Damage Index" was found to be most sensitive and to best indicate a genotoxic hazard. Both species investigated were shown to be sensitive indicators of environmental genotoxicity caused by coal mining activities. In summary, our study constitutes the first investigation of potential genotoxic effects of open coal mining carried out in Puerto Libertador. The investigations provide a guide for measures to evaluate genotoxic hazards, thereby contributing to the development of appropriate measures and regulations for more careful operations during coal mining.

  2. Formation and Human Risk of Carcinogenic Heterocyclic Amines Formed from Natural Precursors in Meat

    Energy Technology Data Exchange (ETDEWEB)

    Knize, M G; Felton, J S

    2004-11-22

    A group of heterocyclic amines that are mutagens and rodent carcinogens form when meat is cooked to medium and well-done states. The precursors of these compounds are natural meat components: creatinine, amino acids and sugars. Defined model systems of dry-heated precursors mimic the amounts and proportions of heterocyclic amines found in meat. Results from model systems and cooking experiments suggest ways to reduce their formation and, thus, to reduce human intake. Human cancer epidemiology studies related to consumption of well-done meat products are listed and compared.

  3. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen?

    Science.gov (United States)

    Surh, Y J; Lee, S S

    1996-03-01

    Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent ingredient of the Capsicum fruits such as hot green and red peppers. Besides its use as a food additive in various spicy cuisines, capsaicin is currently utilized for therapeutic purposes to treat various peripheral painful conditions such as rheumatoid arthritis and diabetic neuropathy. Considering consumption of capsaicin as a food additive and its current medicinal application in humans, correct evaluation and precise assessment of any harmful effects of this compound are essential from the public health standpoint. Numerous investigations have been conducted to determine the potential mutagenic and carcinogenic activity of capsaicin and chili pepper, but results are discordant. This review briefly examines findings in the literature of studies testing mutagenicity and tumorigenicity of capsaicin and presents a possible mechanistic basis for the dual effects exerted by the compound.

  4. In vivo evaluation in rodents of [{sup 123}I]-3-I-CO as a potential SPECT tracer for the serotonin 5-HT{sub 2A} receptor

    Energy Technology Data Exchange (ETDEWEB)

    Blanckaert, Peter B.M. [Laboratory for Radiopharmacy, Ghent University, B-9000 Ghent (Belgium)], E-mail: peter.blanckaert@hotmail.com; Burvenich, Ingrid; Wyffels, Leonie; Bruyne, Sylvie de; Moerman, Lieselotte; Vos, Filip de [Laboratory for Radiopharmacy, Ghent University, B-9000 Ghent (Belgium)

    2008-11-15

    Introduction: [{sup 123}I]-(4-fluorophenyl)[1-(3-iodophenethyl)piperidin-4-yl]methanone ([{sup 123}I]-3-I-CO) is a potential single photon emission computed tomography tracer with high affinity for the serotonin 5-HT{sub 2A} receptor (K{sub i}=0.51 nM) and good selectivity over other receptor (sub)types. To determine the potential of the radioligand as a 5-HT{sub 2A} tracer, regional brain biodistribution and displacement studies will be performed. The influence of P-glycoprotein blocking on the brain uptake of the radioligand will also be investigated. Methods: A regional brain biodistribution study and a displacement study with ketanserin were performed with [{sup 123}I]-3-I-CO. Also, the influence of cyclosporin A (50 mg/kg) on the brain distribution of the radioligand was investigated. For the displacement study, ketanserin (1 mg/kg) was administered 30 min after injection of [{sup 123}I]-3-I-CO. Results: The initial brain uptake of [{sup 123}I]-3-I-CO was quite high, but a rapid wash-out of radioactivity was observed. Cortex-to-cerebellum binding index ratios were low (1.1 - 1.7), indicating considerable aspecific binding and a low specific 'signal' of the radioligand. Tracer uptake was reduced to the levels in cerebellum (a 60% reduction) after ketanserin displacement. Administration of cyclosporin A resulted in a doubling of the brain radioactivity concentration. Conclusions: Although [{sup 123}I]-3-I-CO showed adequate brain uptake and could be displaced by ketanserin, high aspecific binding to brain tissue was responsible for very low cortex-to-cerebellum binding index ratios, possibly limiting the potential of the radioligand as a serotonin 5-HT{sub 2A} receptor tracer. We also demonstrated that [{sup 123}I]-3-I-CO is probably a weak substrate for the P-glycoprotein efflux transporter.

  5. Aquaporins in desert rodent physiology.

    Science.gov (United States)

    Pannabecker, Thomas L

    2015-08-01

    Desert rodents face a sizeable challenge in maintaining salt and water homeostasis due to their life in an arid environment. A number of their organ systems exhibit functional characteristics that limit water loss above that which occurs in non-desert species under similar conditions. These systems include renal, pulmonary, gastrointestinal, nasal, and skin epithelia. The desert rodent kidney preserves body water by producing a highly concentrated urine that reaches a maximum osmolality nearly three times that of the common laboratory rat. The precise mechanism by which urine is concentrated in any mammal is unknown. Insights into the process may be more apparent in species that produce highly concentrated urine. Aquaporin water channels play a fundamental role in water transport in several desert rodent organ systems. The role of aquaporins in facilitating highly effective water preservation in desert rodents is only beginning to be explored. The organ systems of desert rodents and their associated AQPs are described.

  6. DNA Adduct Formation from Metabolic 5'-Hydroxylation of the Tobacco-Specific Carcinogen N'-Nitrosonornicotine in Human Enzyme Systems and in Rats.

    Science.gov (United States)

    Zarth, Adam T; Upadhyaya, Pramod; Yang, Jing; Hecht, Stephen S

    2016-03-21

    N'-Nitrosonornicotine (NNN) is carcinogenic in multiple animal models and has been evaluated as a human carcinogen. NNN can be metabolized by cytochrome P450s through two activation pathways: 2'-hydroxylation and 5'-hydroxylation. While most previous studies have focused on 2'-hydroxylation in target tissues of rats, available evidence suggests that 5'-hydroxylation is a major activation pathway in human enzyme systems, in nonhuman primates, and in target tissues of some other rodent carcinogenicity models. In the study reported here, we investigated DNA damage resulting from NNN 5'-hydroxylation by quantifying the adduct 2-(2-(3-pyridyl)-N-pyrrolidinyl)-2'-deoxyinosine (py-py-dI). In rats treated with NNN in the drinking water (7-500 ppm), py-py-dI was the major DNA adduct resulting from 5'-hydroxylation of NNN in vivo. Levels of py-py-dI in the lung and nasal cavity were the highest, consistent with the tissue distribution of CYP2A3. In rats treated with (S)-NNN or (R)-NNN, the ratios of formation of (R)-py-py-dI to (S)-py-py-dI were not the expected mirror image, suggesting that there may be a carrier for one of the unstable intermediates formed upon 5'-hydroxylation of NNN. Rat hepatocytes treated with (S)- or (R)-NNN or (2'S)- or (2'R)-5'-acetoxyNNN exhibited a pattern of adduct formation similar to that of live rats. In vitro studies with human liver S9 fraction or human hepatocytes incubated with NNN (2-500 μM) demonstrated that py-py-dI formation was greater than the formation of pyridyloxobutyl-DNA adducts resulting from 2'-hydroxylation of NNN. (S)-NNN formed more total py-py-dI adducts than (R)-NNN in human liver enzyme systems, which is consistent with the critical role of CYP2A6 in the 5'-hydroxylation of NNN in human liver. The results of this study demonstrate that the major DNA adduct resulting from NNN metabolism by human enzymes is py-py-dI and provide potentially important new insights into the metabolic activation of NNN in rodents and humans.

  7. Potential of collagen-like triple helical peptides as drug carriers: Their in vivo distribution, metabolism, and excretion profiles in rodents.

    Science.gov (United States)

    Yasui, Hiroyuki; Yamazaki, Chisato M; Nose, Hiroshi; Awada, Chihiro; Takao, Toshifumi; Koide, Takaki

    2013-11-01

    Collagen-model peptides composed of (X-Y-Gly)n sequences were used to study the triple helical structure of collagen. We report the stability of these collagen-like peptides in biological fluids, and their pharmacokinetics including distribution, metabolism, and excretion in animals. A typical collagen-model peptide, H-(Pro-Hyp-Gly)10-OH, was found to be extremely stable in the plasma and distributed mainly in the vascular blood space, and was eliminated through glomerular filtration in the kidneys. Triple helical peptides of (X-Y-Gly)n sequences were quantitatively recovered from the urine of rats after intravenous injection regardless of the differences in peptide net charge between -3 and +6 per triple helix. In contrast, the renal clearance became less efficient when the number of triplet repeats (n) was 12 or more. We also demonstrated the application of a collagen-like triple helical peptide as a novel drug carrier in the blood with a high urinary excretion profile. We further demonstrated that a collagen-like triple helical peptide conjugated to a spin probe, PROXYL, has the potential to evaluate the redox status of oxidative stress-induced animals in vivo.

  8. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis

    Science.gov (United States)

    Ochieng, Josiah; Nangami, Gladys N.; Ogunkua, Olugbemiga; Miousse, Isabelle R.; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T.; Dong, Chenfang; Zhou, Binhua P.; Brown, Dustin G.; Colacci, Annamaria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P.; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Al-Temaimi, Rabeah; Al-Mulla, Fahd; Bisson, William H.; Eltom, Sakina E.

    2015-01-01

    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial–mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. PMID:26106135

  9. Carcinogenicity of syncrudes relative to natural petroleum as assessed by repetative mouse skin application

    Energy Technology Data Exchange (ETDEWEB)

    Holland, J.M.; Whitaker, M.S.; Wesley, J.W.

    1978-01-01

    The relative carcinogenicities of coal and shale derived liquid crudes was compared with a composite blend of natural petroleum using discontinuous exposure of mouse skin. All of the syncrudes were carcinogenic while the natural crude composite was negative following three times weekly application of 50% w/v solutions for 22 wks followed by a 22 wk observation period. In addition to eliciting progressive squamous carcinomas the syncrudes were also capable of inducing persistent ulcerative dermatitis. This inflammatory or necrotizing potential appeared to be inversely proportional to the carcinogenicity of the material. A measure of the relative solubility of the materials in mouse skin was obtained by quantitation of native fluorescence in frozen sections of skin. There appeared to be a general, although non-quantitative association between fluorescence intensity in sebaceous glands and carcinogenicity in epidermal cells, however it will be necessary to examine a greater number of samples to establish such a correlation.

  10. Artificial sweeteners--do they bear a carcinogenic risk?

    Science.gov (United States)

    Weihrauch, M R; Diehl, V

    2004-10-01

    Artificial sweeteners are added to a wide variety of food, drinks, drugs and hygiene products. Since their introduction, the mass media have reported about potential cancer risks, which has contributed to undermine the public's sense of security. It can be assumed that every citizen of Western countries uses artificial sweeteners, knowingly or not. A cancer-inducing activity of one of these substances would mean a health risk to an entire population. We performed several PubMed searches of the National Library of Medicine for articles in English about artificial sweeteners. These articles included 'first generation' sweeteners such as saccharin, cyclamate and aspartame, as well as 'new generation' sweeteners such as acesulfame-K, sucralose, alitame and neotame. Epidemiological studies in humans did not find the bladder cancer-inducing effects of saccharin and cyclamate that had been reported from animal studies in rats. Despite some rather unscientific assumptions, there is no evidence that aspartame is carcinogenic. Case-control studies showed an elevated relative risk of 1.3 for heavy artificial sweetener use (no specific substances specified) of >1.7 g/day. For new generation sweeteners, it is too early to establish any epidemiological evidence about possible carcinogenic risks. As many artificial sweeteners are combined in today's products, the carcinogenic risk of a single substance is difficult to assess. However, according to the current literature, the possible risk of artificial sweeteners to induce cancer seems to be negligible.

  11. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review.

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P; Guyton, Kathryn Z; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane.

    Science.gov (United States)

    Bauman, Julie E; Zang, Yan; Sen, Malabika; Li, Changyou; Wang, Lin; Egner, Patricia A; Fahey, Jed W; Normolle, Daniel P; Grandis, Jennifer R; Kensler, Thomas W; Johnson, Daniel E

    2016-07-01

    Chronic exposure to carcinogens represents the major risk factor for head and neck squamous cell carcinoma (HNSCC). Beverages derived from broccoli sprout extracts (BSE) that are rich in glucoraphanin and its bioactive metabolite sulforaphane promote detoxication of airborne pollutants in humans. Herein, we investigated the potential chemopreventive activity of sulforaphane using in vitro models of normal and malignant mucosal epithelial cells and an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO). Sulforaphane treatment of Het-1A, a normal mucosal epithelial cell line, and 4 HNSCC cell lines led to dose- and time-dependent induction of NRF2 and the NRF2 target genes NQO1 and GCLC, known mediators of carcinogen detoxication. Sulforaphane also promoted NRF2-independent dephosphorylation/inactivation of pSTAT3, a key oncogenic factor in HNSCC. Compared with vehicle, sulforaphane significantly reduced the incidence and size of 4NQO-induced tongue tumors in mice. A pilot clinical trial in 10 healthy volunteers evaluated the bioavailability and pharmacodynamic activity of three different BSE regimens, based upon urinary sulforaphane metabolites and NQO1 transcripts in buccal scrapings, respectively. Ingestion of sulforaphane-rich BSE demonstrated the greatest, most consistent bioavailability. Mucosal bioactivity, defined as 2-fold or greater upregulation of NQO1 mRNA, was observed in 6 of 9 evaluable participants ingesting glucoraphanin-rich BSE; 3 of 6 ingesting sulforaphane-rich BSE; and 3 of 9 after topical-only exposure to sulforaphane-rich BSE. Together, our findings demonstrate preclinical chemopreventive activity of sulforaphane against carcinogen-induced oral cancer, and support further mechanistic and clinical investigation of sulforaphane as a chemopreventive agent against tobacco-related HNSCC. Cancer Prev Res; 9(7); 547-57. ©2016 AACR.

  13. Development of a two-dimensional high-performance liquid chromatography system coupled with on-line reduction as a new efficient analytical method of 3-nitrobenzanthrone, a potential human carcinogen.

    Science.gov (United States)

    Hasei, Tomohiro; Nakanishi, Haruka; Toda, Yumiko; Watanabe, Tetsushi

    2012-08-31

    3-Nitrobenzanthrone (3-NBA) is an extremely strong mutagen and carcinogen in rats inducing squamous cell carcinoma and adenocarcinoma. We developed a new sensitive analytical method, a two-dimensional HPLC system coupled with on-line reduction, to quantify non-fluorescent 3-NBA as fluorescent 3-aminobenzanthrone (3-ABA). The two-dimensional HPLC system consisted of reversed-phase HPLC and normal-phase HPLC, which were connected with a switch valve. 3-NBA was purified by reversed-phase HPLC and reduced to 3-ABA with a catalyst column, packed with alumina coated with platinum, in ethanol. An alcoholic solvent is necessary for reduction of 3-NBA, but 3-ABA is not fluorescent in the alcoholic solvent. Therefore, 3-ABA was separated from alcohol and impurities by normal-phase HPLC and detected with a fluorescence detector. Extracts from surface soil, airborne particles, classified airborne particles, and incinerator dust were applied to the two-dimensional HPLC system after clean-up with a silica gel column. 3-NBA, detected as 3-ABA, in the extracts was found as a single peak on the chromatograms without any interfering peaks. 3-NBA was detected in 4 incinerator dust samples (n=5). When classified airborne particles, that is, those 7.0 μm in size, were applied to the two-dimensional HPLC system after purified using a silica gel column, 3-NBA was detected in those particles with particle sizes NBA in airborne particles and the detection of 3-NBA in incinerator dust. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Oculoscopy in Rabbits and Rodents.

    Science.gov (United States)

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ophthalmic diseases are common in rabbits and rodents. Fast and definitive diagnosis is imperative for successful treatment of ocular diseases. Ophthalmic examination in rabbits and rodents can be challenging. Oculoscopy offers great magnification for the examination of the ocular structures in such animals, including the evaluation of cornea, anterior eye chamber, limbus, iris, lens, and retina. To date, oculoscopy has been described only sporadically and/or under experimental conditions. This article describes the oculoscopy technique, normal and abnormal ocular findings, and the most common eye disorders diagnosed with the aid of endoscopy in rabbits and rodents.

  15. Carcinogenic effects of benzene: Cesare Maltoni's contributions.

    Science.gov (United States)

    Mehlman, Myron A

    2002-12-01

    Cesare Maltoni's contributions to understanding, identifying, and characterizing widely used commercial chemicals in experimental animals are among the most important methods developed in the history of toxicology and serve to protect working men and women, the general population, and our environment from hazardous substances. Maltoni developed experimental methods that have reached the "platinum standard" for protection of public health. Benzene was among the 400 or more chemicals that Maltoni and his associates tested for carcinogenicity. In 1976, Maltoni reported that benzene is a potent experimental carcinogen. Maltoni's experiments clearly demonstrated that benzene is carcinogenic in Sprague-Dawley rats, Wistar rats, Swiss mice, and RF/J mice when administered by inhalation or ingestion. Benzene caused carcinomas of the Zymbal gland, oral cavity, nasal cavities; cancers of the skin, forestomach, mammary glands, and lungs; angiosarcomas and hepatomas of the liver; and hemolymphoreticular cancers. Thus, benzene was shown to be a multipotential carcinogen that produced cancers in several species of animals by various routes of administration. On November 2, 1977, Chemical Week reported that Maltoni provided a "bombshell" when he demonstrated the "first direct link" between benzene and cancer. In this paper, I shall summarize early experiments and human studies and reports; Maltoni's experimental contribution to understanding the carcinogenicity of benzene in humans and animals; earlier knowledge concerning benzene toxicity; and benzene standards and permissible exposure levels.

  16. Cell-mediated mutagenesis by chemical carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Huberman, E.; Langenbach, R.

    1978-01-01

    The cell-mediated mutation system, with the proper choice of metabolizing cells, can be used to detect the mutagenic activities of different classes of chemical carcinogens. When fibroblastic cells were used as the metabolizing cells, a correlation between the in vivo carcinogenic activity and the in vitro mutagenic activity of 11 aromatic polycyclic hydrocarbons was observed. When primary liver cells were used as the metabolizing cells, three known liver carcinogens were demonstrated to be mutagenic by the cell-mediated assay, while two non-carcinogenic analogues were not mutagenic. These results from the cell-mediated system suggest that the reactive intermediates of the carcinogens are stable enough to be transferred from the metabolizing cells to the V79 cells. The cell-mediated mutagenesis system is a simple in vitro assay which may simulate the in vivo situation. It was concluded that this approach could be extended to the co-cultivation of cells from other organs or tissues with mutable mammalian cells.

  17. Carcinogenicity and Immunotoxicity of Embedded Depleted Uranium and Heavy-Metal Tungsten Alloy in Rodents

    Science.gov (United States)

    2006-10-01

    frequency of various types of chromosome aberrations including dicentrics were estimated in first-division metaphase spreads following differential...et al. [Martin 1991] reported that levels of chromosomal aberration, sister chromatid exchange, and dicentrics measured in nuclear fuel workers...metaphase spreads were used for chromosome aberration and SCE analysis respectively, as described below. Genotoxicity - chromosome aberration analysis: The

  18. Histologic Changes as Indicators of Carcinogenicity of Tungsten Alloy in Rodents

    Science.gov (United States)

    2008-01-01

    for example, Cambodia, China, India, Japan, Korea, Malaysia , Pakistan, the Philippine Islands, Thailand, and Vietnam. (Note: Individuals from the...16.44 3 0 + 0 28.61 + 5.72 69.49 + 18.04 6 0 + 0 22.81 + 7.09 77.82 + 10.95 Weight at Euthanasia (g) 1 267.77 + 7.36 300.23 + 5.83 287.12...0.003 0.74 + 0.003 0.77 + 0.003 6 0.72 + 0.004 0.75 + 0.003 0.76 + 0.003 Weight at Euthanasia (g) 1 267.77 + 7.36 300.23 + 5.83 287.12 + 7.49

  19. 78 FR 16681 - International Conference on Harmonisation; Proposed Change to Rodent Carcinogenicity Testing of...

    Science.gov (United States)

    2013-03-18

    ... change to http://www.regulations.gov . Submit written comments to the Division of Dockets Management (HFA... Medicines Agency; and the Japanese Ministry of Health, Labour and Welfare. We would request that CADs be... Dockets Management (see ADDRESSES). It is only necessary to send one set of comments. Identify...

  20. Rodent Control: Seal Up! Trap Up! Clean Up!

    Science.gov (United States)

    ... rodent food sources and nesting sites... Diseases from rodents Diseases directly transmitted by rodents Diseases indirectly transmitted by rodents Cleaning up after rodents Take precautions before and during clean up of ...

  1. Mutagenicity, carcinogenicity and teratogenicity of beryllium.

    Science.gov (United States)

    Léonard, A; Lauwerys, R

    1987-07-01

    The carcinogenicity of a number of beryllium compounds has been confirmed in experiments on laboratory animals and this metal has to be treated as a possible carcinogenic threat to man. These carcinogenic properties are associated with mutagenic activity as shown by the results of short-term tests performed in vitro with beryllium chloride and beryllium sulfate. These soluble beryllium compounds can produce some infidelity of in vitro synthesis, forward gene mutations in microorganisms and in mammalian cells. They are also able to induce cell transformation. In addition to the positive results obtained in several short-term assays beryllium compounds have been found to bind to nucleoproteins, to inhibit certain enzymes needed for DNA synthesis, to bind nucleic acids to cell membranes and to inhibit microtubule polymerization. The teratogenicity of beryllium salts is relatively unknown and needs additional investigation.

  2. The ISS Carcinogens Data Bank (BDC).

    Science.gov (United States)

    Binetti, Roberto; Ceccarelli, Federica; Costamagna, Francesca Marina; D'Angiolini, Antonella; Fabri, Alessandra; Ferri, Maurizio; Riva, Giovanni; Roazzi, Paolo; Trucchi, Daniela; Marcello, Ida

    2008-01-01

    The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanità website, aimed at supporting the risk management decision making of central and local administrators. It can also represent a valuable tool for industry. The available information on carcinogenicity evaluations/classifications produced by European Union and by other institutions (IARC, USEPA, NTP, CCTN) is presented in a concise form accompanied by bibliographic references enabling the users to consult the original sources and, in some cases, to be directly connected to the relevant website. The classifications carried out by each organization in accordance with its own criteria assign the examined agents to specific qualitative categories and do not include quantitative assessment. BDC intends to provide an easy tool for experts, researchers and risk managers dealing with carcinogenic agents.

  3. Regulatory Forum Opinion Piece: Carcinogen Risk Assessment: The Move from Screens to Science.

    Science.gov (United States)

    Downes, Noel; Foster, John

    2015-12-01

    Throughout the last 50 years, the paradigm for carcinogenicity assessment has depended on lifetime bioassays in rodents. Since 1997, the International Conference on Harmonisation (ICH) S1B has permitted the use of a 2-year rodent bioassay (usually in the rat) and an alternative, genetically modified mouse model to support cancer risk assessment of pharmaceuticals. Since its introduction, it has become apparent that many of the stated advantages of the 6-month Tg mouse bioassay have, in actual fact, not been realized, and the concern exists that an albeit imperfect, 2-year mouse bioassay has been replaced by a similarly imperfect 6-month equivalent. This essay argues strongly that model systems, using cancer as the end point, should be discontinued, and that the recent initiatives, from the Organization for Economic Cooperation and Development and Institute of Peace and Conflict Studies, on "mode of action," "adverse outcome pathways," and "human relevance framework" should be embraced as being risk assessments based upon the available science. The recent suggested revisions to the ICH S1 guidelines, utilizing carcinogenicity assessment documents, go some way to developing a science-based risk assessment that does not depend almost entirely on a single, imperfect, cancer-based end point in nonrelevant animal species.

  4. Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.

    Directory of Open Access Journals (Sweden)

    Jarom Heijmans

    Full Text Available Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO to the Apc(Min/+ mouse, a model for spontaneous intestinal polyposis. PRKO-Apc(Min/+ mice exhibited no change in polyp number, size or localization compared to Apc(Min/+. To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis.

  5. A nice book on Italian rodents

    OpenAIRE

    Bellavere C

    2008-01-01

    A recent book on the Italian rodents is presented. The book treats the ecology of rodents as well as more applied topics like the impact of rodents on human activities and the management and control of rodents populations. Written in Italian.

  6. Rodent empathy and affective neuroscience.

    Science.gov (United States)

    Panksepp, Jules B; Lahvis, Garet P

    2011-10-01

    In the past few years, several experimental studies have suggested that empathy occurs in the social lives of rodents. Thus, rodent behavioral models can now be developed to elucidate the mechanistic substrates of empathy at levels that have heretofore been unavailable. For example, the finding that mice from certain inbred strains express behavioral and physiological responses to conspecific distress, while others do not, underscores that the genetic underpinnings of empathy are specifiable and that they could be harnessed to develop new therapies for human psychosocial impairments. However, the advent of rodent models of empathy is met at the outset with a number of theoretical and semantic problems that are similar to those previously confronted by studies of empathy in humans. The distinct underlying components of empathy must be differentiated from one another and from lay usage of the term. The primary goal of this paper is to review a set of seminal studies that are directly relevant to developing a concept of empathy in rodents. We first consider some of the psychological phenomena that have been associated with empathy, and within this context, we consider the component processes, or endophenotypes of rodent empathy. We then review a series of recent experimental studies that demonstrate the capability of rodents to detect and respond to the affective state of their social partners. We focus primarily on experiments that examine how rodents share affective experiences of fear, but we also highlight how similar types of experimental paradigms can be utilized to evaluate the possibility that rodents share positive affective experiences. Taken together, these studies were inspired by Jaak Panksepp's theory that all mammals are capable of felt affective experiences.

  7. Mechanisms of acrylamide induced rodent carcinogenesis.

    Science.gov (United States)

    Klaunig, James E; Kamendulis, Lisa M

    2005-01-01

    Acrylamide is a monomer of polyacrylamide, used in biochemistry, in paper manufacture, in water treatment, and as a soil stabilizer. The monomer can cause several toxic effects and has the potential for human exposure either through the environment or from occupational exposure. Recently, additional concern for the potential toxicity of acrylamide in humans has arisen with the finding of acrylamide formation in some processed foods. It has been established that following chronic exposure, rats exhibited an increase in the incidence of adrenal pheochromocytomas, testicular mesotheliomas, thyroid adenomas and mammary neoplasms in F344 rats. This has raised increased concerns regarding the carcinogenic risk to humans from acrylamide exposure. Studies examining the DNA reactivity of acrylamide have been performed and have had differing results. The tissue and organ pattern of neoplastic development seen in the rat following acrylamide exposure is not consistent with that seen with other strictly DNA reactive carcinogens. Based on the pattern of neoplastic development, it appears that acrylamide is targeting endocrine sensitive tissues. In the current monograph, studies on the effect of acrylamide on DNA reactivity and on altered cell growth in the target tissues in the rat are reported. DNA synthesis was examined in F344 rats treated with acrylamide (0, 2, or 15 mg/kg/day) for 7, 14, or 28 days. Acrylamide increased DNA synthesis in the target tissues (thyroid, testicular mesothelium, adrenal medulla) at all doses and time points examined. In contrast, in a non-target tissue (liver), no increase in DNA synthesis was seen. Examination of DNA damage using single cell gel electrophoresis (the Comet assay) showed an increase in DNA damage in the target tissues, but not in non-target tissue (liver). In addition, a cellular transformation model, (the Syrian Hamster Embryo (SHE) cell morphological transformation model), was used to examine potential mechanisms for the

  8. Use of the modified Ames test as an indicator of the carcinogenicity of residual aromatic extracts

    Energy Technology Data Exchange (ETDEWEB)

    Boogaard, P.; Hedelin, A.; Riley, A.; Rushton, E.; Vaissiere, M.; Minsavage, G.; Rohde, A.; Dalbey, W.

    2013-01-15

    Existing data demonstrate that residual aromatic extracts (RAEs) can be either carcinogenic or non-carcinogenic. CONCAWE had previously concluded that 'Although limited data available indicate that some RAEs are weakly carcinogenic, it is not possible to provide a general recommendation. Classify on a case-by-case basis' (CONCAWE 2005). Therefore CONCAWE's Health/Toxicology Subgroup (H/TSG) has developed a proposal for the use of the modified Ames test as a short-term predictive screening tool for decisions on the classification of RAEs for carcinogenicity. The relationship between RAE chemistry and carcinogenic potential is not as well understood as it is for some other categories of substances, e.g. Other Lubricant Base Oils (OLBO). However, a correlation has been found between the results of the skin carcinogenicity bioassay and the mutagenicity index (MI) obtained from the modified Ames test. Data supporting this correlation are summarised in this report. The H/TSG confirmed that the modified Ames test can be used as a predictive screening tool and that a cut-off value can be established to make a distinction between carcinogenic and non-carcinogenic products. RAEs with a MI > 0.4 demonstrated carcinogenic potential upon dermal application to mouse skin with chronic exposure. RAEs with a MI > 0.4 did not demonstrate a carcinogenic potential. To justify the use of the modified Ames test with RAEs, additional analysis of the repeatability of the test with RAEs was required. With this objective, CONCAWE sponsored a round robin study with different samples of RAEs from member companies, at three different laboratories. The repeatability demonstrated in the round robin study with RAEs support the proposed use of the modified Ames test. As part of the tools available for use by member companies, the H/TSG proposed a standard operating procedure (SOP) (included as an Appendix to this report) on the conduct of the modified Ames test with RAEs. The H

  9. Carcinogenic compounds in alcoholic beverages: an update.

    Science.gov (United States)

    Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

    2016-10-01

    The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

  10. 40 CFR 799.9420 - TSCA carcinogenicity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA carcinogenicity. 799.9420 Section 799.9420 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... their selection. (ii) Age/weight. (A) Testing shall be started with young healthy animals as soon...

  11. Transmission ecology of rodent-borne diseases: New frontiers.

    Science.gov (United States)

    Bordes, Frédéric; Blasdell, Kim; Morand, Serge

    2015-09-01

    Rodents are recognized reservoir hosts for many human zoonotic pathogens. The current trends resulting from anthropocene defaunation suggest that in the future they, along with other small mammals, are likely to become the dominant mammals in almost all human-modified environments. Recent intricate studies on bat-borne emerging diseases have highlighted that many gaps exist in our understanding of the zoonotic transmission of rodent-borne pathogens. This has emphasized the need for scientists interested in rodent-borne diseases to integrate rodent ecology into their analysis of rodent-borne pathogen transmission in order to identify in more detail the mechanisms of spillover and chains of transmission. Further studies are required to better understand the true impact of rodent abundance and the importance of pathogen sharing and circulation in multi-host- multi-pathogen communities. We also need to explore in more depth the roles of generalist and abundant species as the potential links between pathogen-sharing, co-infections and disease transmission.

  12. Plant Secondary Metabolites as Rodent Repellents: a Systematic Review.

    Science.gov (United States)

    Hansen, Sabine C; Stolter, Caroline; Imholt, Christian; Jacob, Jens

    2016-09-01

    The vast number of plant secondary metabolites (PSMs) produced by higher plants has generated many efforts to exploit their potential for pest control. We performed a systematic literature search to retrieve relevant publications, and we evaluated these according to PSM groups to derive information about the potential for developing plant-derived rodent repellents. We screened a total of 54 publications where different compounds or plants were tested regarding rodent behavior/metabolism. In the search for widely applicable products, we recommend multi-species systematic screening of PSMs, especially from the essential oil and terpenoid group, as laboratory experiments have uniformly shown the strongest effects across species. Other groups of compounds might be more suitable for the management of species-specific or sex-specific issues, as the effects of some compounds on particular rodent target species or sex might not be present in non-target species or in both sexes. Although plant metabolites have potential as a tool for ecologically-based rodent management, this review demonstrates inconsistent success across laboratory, enclosure, and field studies, which ultimately has lead to a small number of currently registered PSM-based rodent repellents.

  13. Rodent Species Distribution and Hantavirus Seroprevalence in Residential and Forested areas of Sarawak, Malaysia.

    Science.gov (United States)

    Hamdan, Nur Elfieyra Syazana; Ng, Yee Ling; Lee, Wei Bin; Tan, Cheng Siang; Khan, Faisal Ali Anwarali; Chong, Yee Ling

    2017-01-01

    Rodents belong to the order Rodentia, which consists of three families in Borneo (i.e., Muridae, Sciuridae and Hystricidae). These include rats, mice, squirrels, and porcupines. They are widespread throughout the world and considered pests that harm humans and livestock. Some rodent species are natural reservoirs of hantaviruses (Family: Bunyaviridae) that can cause zoonotic diseases in humans. Although hantavirus seropositive human sera were reported in Peninsular Malaysia in the early 1980s, information on their infection in rodent species in Malaysia is still lacking. The rodent populations in residential and forested areas in Sarawak were sampled. A total of 108 individuals from 15 species of rodents were collected in residential (n = 44) and forested ( n = 64) areas. The species diversity of rodents in forested areas was significantly higher (H = 2.2342) compared to rodents in residential areas (H = 0.64715) (p rodent populations in Sarawak, East Malaysia. The results suggested that hantavirus was not circulating in the studied rodent populations in Sarawak, or it was otherwise at a low prevalence that is below the detection threshold. It is important to remain vigilant because of the zoonotic potential of this virus and its severe disease outcome. Further studies, such as molecular detection of viral genetic materials, are needed to fully assess the risk of hantavirus infection in rodents and humans in this region of Malaysia.

  14. A Field Study of Plague and Tularemia in Rodents, Western Iran.

    Science.gov (United States)

    Mostafavi, Ehsan; Shahraki, Abdolrazagh Hashemi; Japoni-Nejad, Alireza; Esmaeili, Saber; Darvish, Jamshid; Sedaghat, Mohammad Mehdi; Mohammadi, Ali; Mohammadi, Zeinolabedin; Mahmoudi, Ahmad; Pourhossein, Behzad; Ghasemi, Ahmad; Gyuranecz, Miklós; Carniel, Elisabeth

    2017-04-01

    Kurdistan Province in Iran is a historical focus for plague and tularemia. This study aimed at assessing the current status of these two foci by studying their rodent reservoirs. Rodents were trapped and their ectoparasites were collected. The genus and species of both rodents and ectoparasites were determined. Serological analyses of rodent blood samples were done by enzyme-linked immunosorbent assay for plague and by standard tube agglutination assay for tularemia. Rodent spleen samples were subjected to bacterial culture, microscopic examination, and real-time PCR to search for active plague or tularemia infection. During this study, 245 rodents were trapped, of which the most abundant genera were Apodemus (40%), Mus (24.49%), and Meriones (12.65%). One hundred fifty-three fleas, 37 mites, and 54 ticks were collected on these rodents. The results of all direct and indirect tests were negative for plague. Serological tests were positive for tularemia in 4.8% of trapped rodents. This study is the first report on the presence of tularemia infection in rodents in Western Iran. Since Meriones persicus is a known reservoir for plague and tularemia, and this rodent carried plague and tularemia vectors in Marivan and Sanandaj districts, there is a real potential for the occurrence of these two diseases in this region.

  15. Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Ellinger-Ziegelbauer, Heidrun [Bayer Healthcare AG, Department of Molecular and Genetic Toxicology, Aprather Weg 18a, 42096 Wuppertal (Germany)]. E-mail: heidrun.ellinger-ziegelbauer@bayerhealthcare.com; Stuart, Barry [Bayer Crop Science, Department of Toxicology, Stilwell, KS (United States); Wahle, Brad [Bayer Crop Science, Department of Toxicology, Stilwell, KS (United States); Bomann, Werner [Bayer Crop Science, Department of Toxicology, Stilwell, KS (United States); Ahr, Hans Juergen [Bayer Healthcare AG, Department of Molecular and Genetic Toxicology, Aprather Weg 18a, 42096 Wuppertal (Germany)

    2005-08-04

    sufficient to discriminate the two classes of carcinogens, it became evident that combinations of pathway-associated gene expression profiles may be used to predict a genotoxic or nongenotoxic carcinogenic potential of a compound in short-term studies.

  16. [Mapping of carcinogens in the chemical production industry in the province of Ferrara].

    Science.gov (United States)

    Maldotti, M; Spagnolo, M R; Minisci, S; De Rosa, E

    2008-01-01

    This study consists in the reconnaissance of the carcinogenic risk in some processing in Ferrara. The main object is to know, to estimate and to verify the diffusion of the carcinogenic substances and to estimate the number of the exposed or potentially exposed workers. The study has interested the synthesis chemistry and polymer production, woodworking, welding on stainless steel and chromium conversion coating and chrome electroplating. The research has involved 54 factories and 436 workers estimated exposed or potentially exposed to carcinogenic substances. The survey has consisted of inspections in the working places, collection of exposure data, control of the precautionary measures and exposure determination in the case of stainless steel welding. The smallest factories had less knowledge of the risk and for this reason it is necessary to keep constant attention.

  17. Environmental exposure to human carcinogens in teenagers and the association with DNA damage

    DEFF Research Database (Denmark)

    Franken, Carmen; Koppen, Gudrun; Lambrechts, Nathalie

    2017-01-01

    Background We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two...... areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds...... was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP...

  18. Monitoring rodents movements with a biomarker around introduction and feeding foci in an urban environment in Tanzania

    DEFF Research Database (Denmark)

    Mohr, Katrine; Leirs, Herwig; Katakweba, Abdul;

    2007-01-01

    Rodents are of concern as reservoirs and transmitters of pathogens that cause zoonotic and other diseases in domestic animals and humans. The contact between wild and urban rodent fauna is increasing in expanding cities in Africa, and this arguably increases the risk of disease transmission...... to urban populations. When rodents from rural areas are ccidentally introduced into cities and encounter urban rodents, for example, in markets, grain mills and butcheries,   there is a potential that pathogens are transferred between rural and urban rodent populations. Using a non-toxic biomarker......, Rhodamine B (RB), we investigated the distances over which rodents are active around such potential introduction sites. Animals feeding at such sites were traced up to 100 m distant within a period of 10 days.We found that RB is a practical alternative for studying rodent movements. These results may be...

  19. Statistical Comparison of Carcinogenic Effects and Dose-Response Relationships in Rats and Mice for 2,4-Toluene Diamine to those Ascribed to Toluene Diisocyanate

    Science.gov (United States)

    Sielken, Robert L.; Bretzlaff, Robert S.; Valdez-Flores, Ciriaco; Parod, Ralph

    2012-01-01

    The U.S. National Toxicology Program (NTP) conducted 2-year bioassays of commercial grade toluene diisocyanate (TDI) (80% 2,4-TDI and 20% 2,6-TDI) and 2,4-toluene diamine (TDA) and concluded that both were carcinogenic in rodents. In the TDI study, there was an unproven but likely formation of TDA either because of flawed test-substance handling and storage conditions and/or the atypical exposure conditions employed. Although the carcinogenic responses in both studies were qualitatively similar, several statistical analyses were performed to substantiate this possibility more rigorously. Seven different statistical approaches combine to yield a robust and consistent conclusion that, if only a small fraction (approximately 5%) of the dose of TDI were hydrolyzed to TDA in the TDI study, then that would be sufficient to explain the observed carcinogenic responses in the TDI study. PMID:23172986

  20. Toxoplasmosis seroprevalence in urban rodents: a survey in Niamey, Niger

    Science.gov (United States)

    Mercier, Aurélien; Garba, Madougou; Bonnabau, Henri; Kane, Mamadou; Rossi, Jean-Pierre; Dardé, Marie-Laure; Dobigny, Gauthier

    2013-01-01

    A serological survey of Toxoplasma gondii was conducted on 766 domestic and peridomestic rodents from 46 trapping sites throughout the city of Niamey, Niger. A low seroprevalence was found over the whole town with only 1.96% of the rodents found seropositive. However, differences between species were important, ranging from less than 2% in truly commensal Mastomys natalensis, Rattus rattus and Mus musculus, while garden-associated Arvicanthis niloticus displayed 9.1% of seropositive individuals. This is in line with previous studies on tropical rodents - that we reviewed here - which altogether show that Toxoplasma seroprevalence in rodent is highly variable, depending on many factors such as locality and/or species. Moreover, although we were not able to decipher statistically between habitat or species effect, such a contrast between Nile grass rats and the other rodent species points towards a potentially important role of environmental toxoplasmic infection. This would deserve to be further scrutinised since intra-city irrigated cultures are extending in Niamey, thus potentially increasing Toxoplasma circulation in this yet semi-arid region. As far as we are aware of, our study is one of the rare surveys of its kind performed in Sub-Saharan Africa and the first one ever conducted in the Sahel. PMID:23828008

  1. [Carcinogenic activity of the pesticide propoxur].

    Science.gov (United States)

    Pylev, L N; Vasil'eva, L A; Smirnova, O V; Khrustalev, S A; Trukhina, G M

    2010-01-01

    Wistar rats were fed propoxur in their diet at 0, 500, 3000, and 8000 ppm during throughout their life. The number of tumors was equal in the control and experimental groups. These were hemoblastoses and breast and uterine tumors. All tumors occurred spontaneously in the rats. A few experimental animals were found to have bladder epithelial hyperplasia that might be pretumorous; however, no bladder tumors were detected. It is concluded that the investigations revealed no carcinogenic activity of propoxur.

  2. The evolving definition of carcinogenic human papillomavirus

    Directory of Open Access Journals (Sweden)

    Castle Philip E

    2009-05-01

    Full Text Available Abstract Thirteen human papillomavirus (HPV genotypes have been judged to be carcinogenic or probably carcinogenic, and the cause of virtually all cervical cancer worldwide. Other HPV genotypes could possibly be involved. Although the inclusion of possibly carcinogenic HPV genotypes may hurt test specificity, it may indirectly increase the reassurance following a negative HPV test (i.e. the negative predictive value of an HPV test for cervical precancer and cancer. The future of cervical cancer screening in low-resource setting, however, may include once-in-a-lifetime, low-cost and rapid HPV testing. However, the tradeoff of more false positives for greater reassurance may not be acceptable if the local infrastructure cannot manage the screen positives. Now is the time for the community of scientists, doctors, and public health advocates to use the data presented at the 100th International Agency for Research on Cancer monograph meeting to rationally decide the target HPV genotypes for the next generation of HPV tests for use in high-resource and low-resource settings. The implications of including possibly HPV genotypes on HPV test performance, also for guidance on the use of these tests for cervical cancer prevention programs, are discussed.

  3. Oral treatment of rodents with insecticides for control of sand flies (Diptera: Psychodidae) and the fluorescent tracer technique (FTT) as a tool to evaluate potential sand fly control methods.

    Science.gov (United States)

    Mascari, T M; Clark, J; Gordon, S; Mitchell, M A; Rowton, E D; Stout, R; Foil, L D

    2011-03-01

    In laboratory studies, insecticides (diflubenzuron, novaluron, methoprene and, pyriproxyfen) that have been incorporated into rodent diets were effective as feed-throughs against sand fly larvae. Novaluron also was effective against sand fly larvae at low concentrations and under simulated field conditions. Ivermectin has been shown to be effective as a systemic insecticide, killing 100% of blood-feeding sand flies for up to seven d after rodents were treated. The fluorescent tracer technique (FTT) is the use of certain fluorescent dyes (rhodamine B or uranine O) as feed-through transtadial biomarkers for phlebotomine sand flies, systemic biomarkers for blood-feeding sand flies, and permanent markers for nectar-feeding sand flies. The results of these laboratory studies provide proof of concept for the FTT and indicate that the FTT could be used to delineate specific foci with rodent/sand fly associations that would be susceptible to control by using feed-through or systemic insecticides, or foci where insecticide-treated sugar baits could be used against sand flies.

  4. The Ethics of Rodent Control

    NARCIS (Netherlands)

    Meerburg, B.G.; Brom, F.W.A.; Kijlstra, A.

    2008-01-01

    Because western societies generally see animals as objects of moral concern, demands have been made on the way they are treated, e.g. during animal experimentation. In the case of rodent pests, however, inhumane control methods are often applied. This inconsistency in the human-animal relationship r

  5. Forecasting rodent outbreaks in Africa

    DEFF Research Database (Denmark)

    Leirs, Herwig; Verhagen, Ron; Verheyen, Walter

    1996-01-01

    1. Rainfall data were collated for years preceding historical outbreaks of Mastomys rats in East Africa in order to test the hypothesis that such outbreaks occur after long dry periods. 2. Rodent outbreaks were generally not preceded by long dry periods. 3. Population dynamics of Mastomys natalen...

  6. The Ethics of Rodent Control

    NARCIS (Netherlands)

    Meerburg, B.G.; Brom, F.W.A.; Kijlstra, A.

    2008-01-01

    Because western societies generally see animals as objects of moral concern, demands have been made on the way they are treated, e.g. during animal experimentation. In the case of rodent pests, however, inhumane control methods are often applied. This inconsistency in the human-animal relationship

  7. Forecasting rodent outbreaks in Africa

    DEFF Research Database (Denmark)

    Leirs, Herwig; Verhagen, Ron; Verheyen, Walter

    1996-01-01

    natalensis rats in Tanzania are significantly affected by the distribution of rainfall during the rainy season. 4. All previous rodent outbreaks in Tanzania were preceded by abundant rainfall early in the rainy season, i.e, towards the end of the year. 5. A flow chart is constructed to assess the likelihood...

  8. Biomonitoring the Cooked Meat Carcinogen 2-Amino-1-methy-6-phenylimidazo[4,5-b]pyridine in Canine Fur

    OpenAIRE

    Gu, Dan; Neuman, Zachary L.; Modiano, Jaime F.; Turesky, Robert J.

    2012-01-01

    2-Amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) is a heterocyclic aromatic amine (HAA) that is formed during the cooking of meat, poultry, and fish. PhIP is a rodent carcinogen and thought to contribute to several diet-related cancers in humans. PhIP is present in the hair of human omnivores but not in the hair of vegetarians. We have now identified PhIP in the fur of fourteen out of sixteen healthy dogs consuming different brands of commercial pet food. The levels of PhIP in canine f...

  9. 21 CFR 1250.96 - Rodent control.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rodent control. 1250.96 Section 1250.96 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.96 Rodent control. Vessels shall be... of rodent control....

  10. Rodent Oncology: Diseases, Diagnostics, and Therapeutics.

    Science.gov (United States)

    Hocker, Samuel E; Eshar, David; Wouda, Raelene M

    2017-01-01

    Cancer incidence in rodent species varies dramatically from a common occurrence in mice and rats to just a limited number of documented cases in chinchillas and degus. This article summarizes common tumors, both benign and malignant, that have been reported to occur in rodents. Outlined are clinical signs, diagnostics, and treatments that have been described for rodents presenting with specific neoplasms.

  11. Is dermatologic usage of coal tar carcinogenic? A review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Pion, I.A.; Koenig, K.L.; Lim, H.W. [New York VA Medical Center, New York, NY (United States)

    1995-03-01

    Coal tar ointments have been used for decades in the treatment of various dermatoses, most notably eczema and psoriasis. Occupational exposure to coal tar poses an increased risk of developing cutaneous malignancies. The evidence of an increased risk of skin cancer in humans, as a result of dermatologic usage of tar, however, is conflicting. A consensus on the carcinogenicity of tar was sought. The existing literature (in vitro, animal and human studies) on this subject was reviewed. The carcinogenicity of coal tar was clearly demonstrated by in vitro and animal studies, and appears to be potentiated by concomitant use of ultraviolet radiation. Systemic absorption of mutagens from topically applied tar has been demonstrated in humans. Epidemiologic studies in humans, however, have not definitively shown an increase in skin cancer with therapeutic use of tar. Conclusive evidence for the carcinogenicity of tar used in dermatologic practice is lacking. Further controlled studies are necessary. 49 refs., 1 tab.

  12. Evidence supporting product standards for carcinogens in smokeless tobacco products.

    Science.gov (United States)

    Hatsukami, Dorothy K; Stepanov, Irina; Severson, Herb; Jensen, Joni A; Lindgren, Bruce R; Horn, Kimberly; Khariwala, Samir S; Martin, Julia; Carmella, Steven G; Murphy, Sharon E; Hecht, Stephen S

    2015-01-01

    Smokeless tobacco products sold in the United States vary significantly in yields of nicotine and tobacco-specific nitrosamines (TSNA). With the passage of the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration now has the authority to establish product standards. However, limited data exist determining the relative roles of pattern of smokeless tobacco use versus constituent levels in the smokeless tobacco product in exposure of users to carcinogens. In this study, smokeless tobacco users of brands varying in nicotine and TSNA content were recruited from three different regions in the U.S. Participants underwent two assessment sessions. During these sessions, demographic and smokeless tobacco use history information along with urine samples to assess biomarkers of exposure and effect were collected. During the time between data collection, smokeless tobacco users recorded the amount and duration of smokeless tobacco use on a daily basis using their diary cards. Results showed that independent of pattern of smokeless tobacco use and nicotine yields, levels of TSNA in smokeless tobacco products played a significant role in carcinogen exposure levels. Product standards for reducing levels of TSNA in smokeless tobacco products are necessary to decrease exposure to these toxicants and potentially to reduce risk for cancer.

  13. Carcinogenic effects ofcircadian disruption:an epigenetic viewpoint

    Institute of Scientific and Technical Information of China (English)

    Abbas Salavaty

    2015-01-01

    Circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, affects many biological processes within the body and results in different long-term diseases, including cancer. Circadian regulatory pathways result in rhythmic epigenetic modiifcations and the formation of circadian epigenomes. Aberrant epigenetic modiifcations, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic effects of circadian disruption. In this review, I ifrst discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modiifcations that result in circadian disruption. In addition, I explain the carcinogenic effects of circadian disruption and highlight its potential role in different human cancers using an epigenetic view-point. Finally, the importance of chronotherapy in cancer treatment is highlighted.

  14. Carcinogenic effects of circadian disruption: an epigenetic viewpoint.

    Science.gov (United States)

    Salavaty, Abbas

    2015-08-08

    Circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, affects many biological processes within the body and results in different long-term diseases, including cancer. Circadian regulatory pathways result in rhythmic epigenetic modifications and the formation of circadian epigenomes. Aberrant epigenetic modifications, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic effects of circadian disruption. In this review, I first discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modifications that result in circadian disruption. In addition, I explain the carcinogenic effects of circadian disruption and highlight its potential role in different human cancers using an epigenetic viewpoint. Finally, the importance of chronotherapy in cancer treatment is highlighted.

  15. Euthanasia using gaseous agents in laboratory rodents.

    Science.gov (United States)

    Valentim, A M; Guedes, S R; Pereira, A M; Antunes, L M

    2016-08-01

    Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously. Nevertheless, its aversive potential has been criticized in terms of animal welfare. The data available regarding the use of carbon dioxide (CO2), inhaled anaesthetics (such as isoflurane, sevoflurane, halothane and enflurane), as well as carbon monoxide and inert gases are discussed throughout this review. Euthanasia of fetuses and neonates is also addressed. A table listing currently available information to ease access to data regarding euthanasia techniques using gaseous agents in laboratory rodents was compiled. Regarding better animal welfare, there is currently insufficient evidence to advocate banning or replacing CO2 in the euthanasia of rodents; however, there are hints that alternative gases are more humane. The exposure to a volatile anaesthetic gas before loss of consciousness has been proposed by some scientific studies to minimize distress; however, the impact of such a measure is not clear. Areas of inconsistency within the euthanasia literature have been highlighted recently and stem from insufficient knowledge, especially regarding the advantages of the administration of isoflurane or sevoflurane over CO2, or other methods, before loss of consciousness. Alternative methods to minimize distress may include the development of techniques aimed at inducing death in the home cage of animals. Scientific outcomes have to be considered before choosing the most suitable euthanasia method to obtain the best results and accomplish the 3Rs (replacement, reduction and refinement).

  16. Prenatal stressors in rodents: Effects on behavior

    Directory of Open Access Journals (Sweden)

    Marta Weinstock

    2017-02-01

    Full Text Available The current review focuses on studies in rodents published since 2008 and explores possible reasons for any differences they report in the effects of gestational stress on various types of behavior in the offspring. An abundance of experimental data shows that different maternal stressors in rodents can replicate some of the abnormalities in offspring behavior observed in humans. These include, anxiety, in juvenile and adult rats and mice, assessed in the elevated plus maze and open field tests and depression, detected in the forced swim and sucrose-preference tests. Deficits were reported in social interaction that is suggestive of pathology associated with schizophrenia, and in spatial learning and memory in adult rats in the Morris water maze test, but in most studies only males were tested. There were too few studies on the novel object recognition test at different inter-trial intervals to enable a conclusion about the effect of prenatal stress and whether any deficits are more prevalent in males. Among hippocampal glutamate receptors, NR2B was the only subtype consistently reduced in association with learning deficits. However, like in humans with schizophrenia and depression, prenatal stress lowered hippocampal levels of BDNF, which were closely correlated with decreases in hippocampal long-term potentiation. In mice, down-regulation of BDNF appeared to occur through the action of gene-methylating enzymes that are already increased above controls in prenatally-stressed neonates. In conclusion, the data obtained so far from experiments in rodents lend support to a physiological basis for the neurodevelopmental hypothesis of schizophrenia and depression.

  17. The role of rodents in avian influenza outbreaks in poultry farms: a review.

    Science.gov (United States)

    Velkers, Francisca C; Blokhuis, Simon J; Veldhuis Kroeze, Edwin J B; Burt, Sara A

    2017-12-01

    Wild migratory birds are associated with global avian influenza virus (AIV) spread. Although direct contact with wild birds and contaminated fomites is unlikely in modern non-free range poultry farms applying biosecurity measures, AIV outbreaks still occur. This suggests involvement of other intermediate factors for virus transmission between wild birds and poultry. This review describes current evidence of the potential role of rodents in AIV transmission from wild birds to poultry and between poultry houses. Rodents can be abundant around poultry houses, share their habitat with waterfowl and can readily enter poultry houses. Survival of AIV from waterfowl in poultry house surroundings and on the coat of rodents suggests that rodents are likely to act as mechanical vector. AIVs can replicate in rodents without adaptation, resulting in high viral titres in lungs and nasal turbinates, virus presence in nasal washes and saliva, and transmission to naïve contact animals. Therefore, active AIV shedding by infected rodents may play a role in transmission to poultry. Further field and experimental studies are needed to provide evidence for a role of rodents in AIV epidemiology. Making poultry houses rodent-proof and the immediate surroundings unattractive for rodents are recommended as preventive measures against possible AIV introduction.

  18. Characteristics associated with contact with rodents in, around, and outside homes in Khon Kaen Province, Thailand.

    Science.gov (United States)

    Suwannarong, Kanokwan; Chapman, Robert S

    2015-04-01

    Rodents are an important reservoir for zoonotic diseases. To enhance the evidence on the human-rodent interface, this cross-sectional study was conducted in 2011 to investigate characteristics associated with rodent contact in Khon Kaen Province, Thailand. A standardized, interviewer-administered questionnaire elicited information from 201 adults (101 males and 100 females). Overall, 86.6% of participants reported encountering or seeing evidence of rodents in or near the home, whereas 57.2% encountered rodents while working with crops. Encountering rodents in or near the home was positively associated with the number of agricultural activities, whereas encountering rodents during crop work was positively associated with perceiving that disease can be acquired from rodents, the number of food crops grown, the number of agricultural activities, and living in a house with wooden walls. Surprisingly, neither outcome was associated appreciably with gender, age, or setting (urban, forest, or agricultural). These results provide information on the potential risk of rodent-borne zoonoses; this evidence has implications for risk communication strategies in this province and likely elsewhere.

  19. Carcinogenicity of consumption of red and processed meat: What about environmental contaminants?

    Science.gov (United States)

    Domingo, José L; Nadal, Martí

    2016-02-01

    In October 26, 2015, the International Agency for Research on Cancer (IARC) issued a press release informing of the recent evaluation of the carcinogenicity of red and processed meat consumption. The consumption of red meat and processed meat was classified as "probably carcinogenic to humans", and as "carcinogenic to humans", respectively. The substances responsible of this potential carcinogenicity would be generated during meat processing, such as curing and smoking, or when meat is heated at high temperatures (N-nitroso-compounds, polycyclic aromatic hydrocarbons and heterocyclic aromatic amines). However, in its assessments, the IARC did not make any reference to the role that may pose some carcinogenic environmental pollutants, which are already present in raw or unprocessed meat. The potential role of a number of environmental chemical contaminants (toxic trace elements, polycyclic aromatic hydrocarbons, polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated biphenyls, polybrominated diphenyl ethers, polychlorinated diphenyl ethers, polychlorinated naphthalenes and perfluoroalkyl substances) on the carcinogenicity of consumption of meat and meat products is discussed in this paper. A case-study, Catalonia (Spain), is specifically assessed, while the influence of cooking on the concentrations of environmental pollutants is also reviewed. It is concluded that although certain cooking processes could modify the levels of chemical contaminants in food, the influence of cooking on the pollutant concentrations depends not only on the particular cooking process, but even more on their original contents in each specific food item. As most of these environmental pollutants are organic, cooking procedures that release or remove fat from the meat should tend to reduce the total concentrations of these contaminants in the cooked meat. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M. [New York Medical College, Department of Pathology, Valhalla (United States); Ahr, Hans-Juergen; Schmidt, Ulrich [Bayer AG, Institute of Toxicology, Wuppertal (Germany); Enzmann, Harald H. [Federal Institute for Drugs and Medical Devices, Bonn (Germany)

    2004-10-01

    Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using {sup 32}P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had {sup 32}P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

  1. Population cycles in small rodents.

    Science.gov (United States)

    Krebs, C J; Gaines, M S; Keller, B L; Myers, J H; Tamarin, R H

    1973-01-05

    colonizing ability are called r strategists because they have high reproductive potential and are able to exploit a new environment rapidly. Dispersing voles seem to be r strategists. Young females in breeding condition were over-represented in dispersing female Microtus (17). The Tf(C)/Tf(E) females, which were more common among dispersers during the phase of population increase (Fig. 6), also have a slight reproductive advantage over the other Tf genotypes (19). Thus in Microtus populations the animals with the highest reproductive potential, the r strategists, are dispersing. The segment of the population which remains behind after the selection-via-dispersal are those individuals which are less influenced by increasing population densities. These are the individuals which maximize use of the habitat, the K strategists in MacArthur and Wilson's terminology, or voles selected for spacing behavior. Thus we can describe population cycles in Microtus in the same theoretical framework as colonizing species on islands. Our work on Microtus is consistent with the hypothesis of genetic and behavioral effects proposed by Chitty (6) (Fig. 7) in that it shows both behavioral differences in males during the phases of population fluctuation and periods of strong genetic selection. The greatest gaps in our knowledge are in the area of genetic-behavioral interactions which are most difficult to measure. We have no information on the heritability of aggressive behavior in voles. The pathways by which behavioral events are translated into physiological changes which affect reproduction and growth have been carefully analyzed by Christian and his associates (28) for rodents in laboratory situations, but the application of these findings to the complex field events described above remains to be done. Several experiments are suggested by our work. First, other populations of other rodent species should increase to abnormal densities if enclosed in a large fenced area (29). We need to find

  2. Report on carcinogens monograph on cumene.

    Science.gov (United States)

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers.

  3. Autoclave sterilization produces acrylamide in rodent diets: implications for toxicity testing.

    Science.gov (United States)

    Twaddle, Nathan C; Churchwell, Mona I; McDaniel, L Patrice; Doerge, Daniel R

    2004-06-30

    Acrylamide (AA) is a neurotoxic and carcinogenic contaminant that is formed during the cooking of starchy foods. Assessment of human risks from toxicants is routinely performed using laboratory rodents, and such testing requires careful control of unintended exposures, particularly through the diet. This study describes an analytical method based on liquid chromatography with electrospray tandem mass spectrometry that was used to measure endogenous AA in rodent diets and to survey a number of commercial products for contamination. Method sensitivity permitted accurate quantification of endogenous levels of AA in raw diets below 20 ppb. Autoclaving a standard rodent diet (NIH-31) increased the AA content 14-fold, from 17 to 240 ppb. A nutritionally equivalent diet that was sterilized by irradiation was found to contain approximately 10 ppb of AA (NIH-31IR). A toxicokinetic study of AA and its epoxide metabolite, glycidamide, was performed by switching mice from NIH-31IR to the autoclaved diet for a 30 min feeding period (average AA dose administered was 4.5 microg/kg of body weight). The concentrations of AA and glycidamide were measured in serum collected at various times. The elimination half-lives and the areas under the respective concentration-time curves were similar for AA and glycidamide. Mice maintained on autoclaved NIH-31 diet, but otherwise untreated, showed elevated steady state levels of a glycidamide-derived DNA adduct in liver relative to mice maintained on the irradiated diet. This study demonstrates that a heat sterilization procedure used in laboratory animal husbandry (i.e., autoclaving) can lead to the formation of significant levels of AA in basal diets used for toxicity testing. AA in rodent diets is bioavailable, is distributed to tissues, and is metabolically activated to a genotoxic metabolite, which produces quantifiable cumulative DNA damage. Although the contribution of endogenous AA to the incidence of tumors in multiple organs of

  4. Comparison of rat olfactory mucosal responses to carcinogenic and non-carcinogenic chloracetanilides

    Science.gov (United States)

    Genter, M.B.; Warner, B.M.; Medvedovic, M.; Sartor, M.A.

    2009-01-01

    Alachlor and butachlor are chloracetanilide herbicides that induce olfactory tumors in rats, whereas propachlor does not. The mechanism by which alachlor induces tumors is distinct from many other nasal carcinogens, in that alachlor induces a gradual de-differentiation of the olfactory mucosa (OM) to a more respiratory-like epithelium, in contrast to other agents that induce cytotoxicity, followed by an aberrant regenerative response. We studied biochemical and genomic effects of these compounds to identify processes that occur in common between alachlor- and butachlor-treated rats. Because we have previously shown that matrix metalloproteinase-2 (MMP2) is activated in OM by alachlor, in the present studies we evaluated both MMP2 activation and changes in OM gene expression in response to carcinogenic and non-carcinogenic chloracetanilide treatments. All three chloracetanilides activated MMP2, and > 300 genes were significantly up- or downregulated between control and alachlor-treated rats. The most significantly regulated gene was vomeromodulin, which was dramatically upregulated by alachlor and butachlor treatment (>60-fold), but not by propachlor treatment. Except for similar gene responses in alachlor- and butachlor-treated rats, we did not identify clear-cut differences that would predict OM carcinogenicity in this study. PMID:19425180

  5. The OSIRIS Weight of Evidence approach: ITS mutagenicity and ITS carcinogenicity.

    Science.gov (United States)

    Buist, Harrie; Aldenberg, Tom; Batke, Monika; Escher, Sylvia; Klein Entink, Rinke; Kühne, Ralph; Marquart, Hans; Pauné, Eduard; Rorije, Emiel; Schüürmann, Gerrit; Kroese, Dinant

    2013-11-01

    Risk assessment of chemicals usually implies data evaluation of in vivo tests in rodents to conclude on their hazards. The FP7 European project OSIRIS has developed integrated testing strategies (ITS) for relevant toxicological endpoints to avoid unnecessary animal testing and thus to reduce time and costs. This paper describes the implementation of ITS mutagenicity and carcinogenicity in the public OSIRIS webtool. The data requirements of REACH formed the basis for these ITS. The main goal was to implement procedures to reach a conclusion on the adequacy and validity of available data. For the mutagenicity ITS a quantitative Weight of Evidence approach based on Bayesian statistics was developed and implemented. The approach allows an overall quality assessment of all available data for the five types of mutagenicity data requirements: in vitro bacterial mutagenicity, in vitro and in vivo chromosome aberration, in vitro and in vivo mammalian mutagenicity. For the carcinogenicity ITS a tool was developed to evaluate the quality of studies not conforming (entirely) to guidelines. In a tiered approach three quality aspects are assessed: documentation (reliability), study design (adequacy) and scope of examination (validity). The quality assessment is based on expert and data driven quantitative Weight of Evidence.

  6. Occurrence, uses, and carcinogenicity of arylamines.

    Science.gov (United States)

    Chung, King-Thom

    2015-01-01

    Arylamines are chemically synthesized and contained in oxidants, epoxy polymers, explosives, fungicides, pesticides, colorants, polyurethanes, and used in rubber, pharmacology, cosmetics, and other chemical industries. Many arylamines are ubiquitously present in cigarette smoke, cooking fume hoods, foods, automobile exhaust, industrial sites, etc. Some arylamines can be generated through azo reduction by intestinal, skin, and environmental microorganisms from azo dyes that are widely used. Arylamines can also be generated by reduction of the nitro-group containing polyhydrated hydrocarbons including muntions. Some arylamines are released by burning nitrogen containing organic materials at high temperatures. Some medical drugs are also arylamines. Furthermore, many arylamines are essential constituents of normal metabolism or the result of abnormal metabolism or dietary sources. Some arylamines are mutagenic, carcinogenic or the cause of other kinds of maladies. Some arylamine are considered the major etiological agents of bladder tumors in humans and animals but may also induce other types of cancers in various organs. The organ, tissue, and species specificity of the arylamine-inducing carcinogenesis may be determined by their availability, distribution, and the presence of metabolic activation/detoxicification enzymes of each organ or tissue of different species. The ubiquitous arylamines, therefore, pose serious hazards to human health and environment. This article will address the occurrence, uses, carcinogenicity, and other arylamines-induced diseases.

  7. Tobacco carcinogens, their biomarkers and tobacco-induced cancer.

    Science.gov (United States)

    Hecht, Stephen S

    2003-10-01

    The devastating link between tobacco products and human cancers results from a powerful alliance of two factors - nicotine and carcinogens. Without either one of these, tobacco would be just another commodity, instead of being the single greatest cause of death due to preventable cancer. Nicotine is addictive and toxic, but it is not carcinogenic. This addiction, however, causes people to use tobacco products continually, and these products contain many carcinogens. What are the mechanisms by which this deadly combination leads to 30% of cancer-related deaths in developed countries, and how can carcinogen biomarkers help to reveal these mechanisms?

  8. Prediction of Non-Genotoxic Carcinogenicity Based on Genetic Profiles of Short Term Exposure Assays

    Science.gov (United States)

    Pérez, Luis Orlando; González-José, Rolando; García, Pilar Peral

    2016-01-01

    Non-genotoxic carcinogens are substances that induce tumorigenesis by non-mutagenic mechanisms and long term rodent bioassays are required to identify them. Recent studies have shown that transcription profiling can be applied to develop early identifiers for long term phenotypes. In this study, we used rat liver expression profiles from the NTP (National Toxicology Program, Research Triangle Park, USA) DrugMatrix Database to construct a gene classifier that can distinguish between non-genotoxic carcinogens and other chemicals. The model was based on short term exposure assays (3 days) and the training was limited to oxidative stressors, peroxisome proliferators and hormone modulators. Validation of the predictor was performed on independent toxicogenomic data (TG-GATEs, Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System, Osaka, Japan). To build our model we performed Random Forests together with a recursive elimination algorithm (VarSelRF). Gene set enrichment analysis was employed for functional interpretation. A total of 770 microarrays comprising 96 different compounds were analyzed and a predictor of 54 genes was built. Prediction accuracy was 0.85 in the training set, 0.87 in the test set and increased with increasing concentration in the validation set: 0.6 at low dose, 0.7 at medium doses and 0.81 at high doses. Pathway analysis revealed gene prominence of cellular respiration, energy production and lipoprotein metabolism. The biggest target of toxicogenomics is accurately predict the toxicity of unknown drugs. In this analysis, we presented a classifier that can predict non-genotoxic carcinogenicity by using short term exposure assays. In this approach, dose level is critical when evaluating chemicals at early time points. PMID:27818731

  9. Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based nanoparticles

    Science.gov (United States)

    MAGAYE, RUTH; ZHAO, JINSHUN; BOWMAN, LINDA; DING, MIN

    2012-01-01

    The nanotechnology industry has matured and expanded at a rapid pace in the last decade, leading to the research and development of nanomaterials with enormous potential. The largest source of these nanomaterials is the transitional metals. It has been revealed that numerous properties of these nano-sized elements are not present in their bulk states. The nano size of these particles means they are easily transported into biological systems, thus, raising the question of their effects on the susceptible systems. Although advances have been made and insights have been gained on the effect of transitional metals on susceptible biological systems, there still is much ground to be covered, particularly with respect to our knowledge on the genotoxic and carcinogenic effects. Therefore, this review intends to summarize the current knowledge on the genotoxic and carcinogenic potential of cobalt-, nickel- and copper-based nanoparticles indicated in in vitro and in vivo mammalian studies. In the present review, we briefly state the sources, use and exposure routes of these nanoparticles and summarize the current literature findings on their in vivo and in vitro genotoxic and carcinogenic effects. Due to the increasing evidence of their role in carcinogenicity, we have also included studies that have reported epigenetic factors, such as abnormal apoptosis, enhanced oxidative stress and pro-inflammatory effects involving these nanoparticles. PMID:23170105

  10. DNA adducts of the tobacco carcinogens 2-amino-9H-pyrido[2,3-b]indole and 4-aminobiphenyl are formed at environmental exposure levels and persist in human hepatocytes.

    Science.gov (United States)

    Nauwelaërs, Gwendoline; Bellamri, Medjda; Fessard, Valérie; Turesky, Robert J; Langouët, Sophie

    2013-09-16

    Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25-100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ∼5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a 10,000-fold concentration range (1 nM-10 μM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes suggest that AαC can contribute to DNA damage

  11. Rodent consumption in Khon Kaen Province, Thailand.

    Science.gov (United States)

    Suwannarong, Kanokwan; Chapman, Robert S

    2014-09-01

    Rodents are important reservoirs of rodent-borne infections worldwide, including Southeast Asia and Northeast Thailand (Isaan), where rodent consumption may be a source of rodent-borne diseases. The behavior of consuming rodents is related to a population's traditions, knowledge, cultural, and household contexts, among other factors. This cross-sectional survey was conducted in Khon Kaen Province, Thailand during November-December 2011. It aimed to elicit information about rodent consumption among residents of this province, and to identify factors associated with rodent consumption there. Multiple logistic regression analysis indicated that male gender, large family size, and use of rainwater as the main source of drinking water were positively associated with reported rodent consumption in this province, while having proper knowledge/attitudes towards animal-borne disease was negatively associated. These results provide evidence-base information for further studies, such as participatory ac- tion research, to further explore how people interact with rodents in different contexts. Further research is also needed to characterize risk of zoonotic diseases in relation to rodent consumption.

  12. Review article : anthranoid laxatives and their potential carcinogenic effects

    NARCIS (Netherlands)

    van Gorkom, B A; de Vries, E G; Karrenbeld, A; Kleibeuker, J H

    1999-01-01

    Anthranoid laxatives are widely used laxatives of natural origin, Because of their chemical structure they are carried unabsorbed to the large bowel, where metabolism to the active aglycones takes place, These aglycones exert their laxative effect by damaging epithelial cells, which leads directly a

  13. A Web-based Simulator for Sample Size and Power Estimation in Animal Carcinogenicity Studies

    Directory of Open Access Journals (Sweden)

    Hojin Moon

    2002-12-01

    Full Text Available A Web-based statistical tool for sample size and power estimation in animal carcinogenicity studies is presented in this paper. It can be used to provide a design with sufficient power for detecting a dose-related trend in the occurrence of a tumor of interest when competing risks are present. The tumors of interest typically are occult tumors for which the time to tumor onset is not directly observable. It is applicable to rodent tumorigenicity assays that have either a single terminal sacrifice or multiple (interval sacrifices. The design is achieved by varying sample size per group, number of sacrifices, number of sacrificed animals at each interval, if any, and scheduled time points for sacrifice. Monte Carlo simulation is carried out in this tool to simulate experiments of rodent bioassays because no closed-form solution is available. It takes design parameters for sample size and power estimation as inputs through the World Wide Web. The core program is written in C and executed in the background. It communicates with the Web front end via a Component Object Model interface passing an Extensible Markup Language string. The proposed statistical tool is illustrated with an animal study in lung cancer prevention research.

  14. Combining QSAR modeling and text-mining techniques to link chemical structures and carcinogenic modes of action

    Directory of Open Access Journals (Sweden)

    Georgios Papamokos

    2016-08-01

    Full Text Available There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. QSAR, a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  15. Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the k sub e test

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, M.L. (ed.); Bakale, G.; McCreary, R.D.

    1989-01-01

    The interdependence of the electrophilic and carcinogenic properties of chemicals that was demonstrated two decades ago rekindled interest in the somatic mutation theory of carcinogenesis. Interest in this theory grew with the development of a reverse-mutation bacterial assay in the laboratory of B.N. Ames that permitted the mutagenic properties of the chemicals to be determined quickly and yielded results which indicated that carcinogens are mutagens.'' Subsequent validation studies of this bioassay, the Salmonella typhimurium/microsome or Ames test,'' by Ames' group and others provided additional support for the correlation between mutagenicity and carcinogenicity which led to the worldwide deployment of the Ames test in thousands of laboratories and to the development of more than 100 other short-term tests that continue to be used to identify potential carcinogens via various end-points of genotoxicity. This document discusses electrophilicity, mutagenicity, and carcinogenicity relationships as well as carcinogen-screening of chemicals. 28 refs., 4 tabs.

  16. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  17. Molecular basis of carcinogenicity of tungsten alloy particles

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Robert M.; Williams, Tim D.; Waring, Rosemary H.; Hodges, Nikolas J., E-mail: n.hodges@bham.ac.uk

    2015-03-15

    The tungsten alloy of 91% tungsten, 6% nickel and 3% cobalt (WNC 91–6–3) induces rhabdomyosarcoma when implanted into a rat thigh muscle. To investigate whether this effect is species-specific human HSkMc primary muscle cells were exposed to WNC 91–6–3 particles and responses were compared with those from a rat skeletal muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was measured and oligonucleotide microarrays were used for transcriptional profiling. WNC 91–6–3 particles caused toxicity in cells adjacent to the particles and also increased DNA strand breaks. Inhibition of caspase 3 by WNC 91–6–3 occurred in rat but not in human cells. In both rat and human cells, the transcriptional response to WNC 91–6–3 showed repression of transcripts encoding muscle-specific proteins with induction of glycolysis, hypoxia, stress responses and transcripts associated with DNA damage and cell death. In human cells, genes encoding metallothioneins were also induced, together with genes related to angiogenesis, dysregulation of apoptosis and proliferation consistent with pre-neoplastic changes. An alloy containing iron, WNF 97–2–1, which is non-carcinogenic in vivo in rats, did not show these transcriptional changes in vitro in either species while the corresponding cobalt-containing alloy, WNC 97–2–1 elicited similar responses to WNC 91–6–3. Tungsten alloys containing both nickel and cobalt therefore have the potential to be carcinogenic in man and in vitro assays coupled with transcriptomics can be used to identify alloys, which may lead to tumour formation, by dysregulation of biochemical processes. - Highlights: • Use of transcriptomics to identify likely carcinogenic tungsten alloys in vitro • Cobalt containing alloys cause oxidative stress, DNA-damage and perturb apoptosis. • Presence of cobalt causes changes in gene expression

  18. Can creatine supplementation form carcinogenic heterocyclic amines in humans?

    Science.gov (United States)

    Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

    2015-09-01

    the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens.

  19. Anti-erosion stone bunds influence rodent dynamics and crop damage in Ethiopian highlands

    Science.gov (United States)

    Meheretu, Yonas; Welegerima, Kiros; Teferi, Mekonen; Yirga, Gidey; Haile, Mitiku; Sluydts, Vincent; Bauer, Hans; Nyssen, Jan; Deckers, Jozef; Leirs, Herwig

    2014-05-01

    In areas of subsistence agriculture, a variety of soil conservation methods have been implemented in the last few decades to improve crop yields, however these can have unintended consequences such as providing habitat for rodent pests. We studied rodent population dynamics and estimated crop damage in high and low stone bund density fields for four cropping seasons in Tigray highlands, northern Ethiopia. Stone bunds are physical structures for soil and water conservation, and potentially habitat for rodents. We used a general model to relate the proportion of crop damage to rodent abundance, stone bund density and crop stages. We found a positive correlation between rodent abundance and crop damage, and significant variation in rodent abundance and crop damage between high and low stone bund density fields. Furthermore, crop damage also varied significantly between crop stages. We concluded that Mastomys awashensis and Arvicanthis dembeensis were the two most important crop pests in the highlands causing significant damage. Fields with high stone bund density (~10 m average distance apart) harbor more rodents and endure a significantly higher proportion of crop damage compared to fields with lower stone bund density (~15 m average distance apart). The fact that rodent abundances peaked during the reproductive stage of the crop and around harvest implies the need for management intervention before these crop stages are attained.

  20. Development of a screening tool to prioritize testing for the carcinogenic hazard of residual aromatic extracts and related petroleum streams.

    Science.gov (United States)

    Goyak, Katy O; Kung, Ming H; Chen, Min; Aldous, Keith K; Freeman, James J

    2016-12-15

    Residual aromatic extracts (RAE) are petroleum substances with variable composition predominantly containing aromatic hydrocarbons with carbon numbers greater than C25. Because of the high boiling nature of RAEs, the aromatics present are high molecular weight, with most above the range of carcinogenic polycyclic aromatic hydrocarbons (PAHs). However, refinery distillations are imperfect; some PAHs and their heteroatom-containing analogs (collectively referred to as polycyclic aromatic content or PAC) may remain in the parent stream and be extracted into the RAE, and overall PAC content is related to the carcinogenic potential of an RAE. We describe here a real-time analytical chemistry-based tool to assess the carcinogenic hazard of RAE via the development of a functional relationship between carcinogenicity and boiling point. Samples representative of steps along the RAE manufacturing process were obtained from five refineries to evaluate relationships between mutagenicity index (MI), PAC ring content and gas chromatographic distillation (GCD) curves. As expected, a positive linear relationship between MI and PAC ring content occurred, most specifically for 3-6 ring PAC (R(2)=0.68). A negative correlation was found between MI and temperature at 5% vaporization by GCD (R(2)=0.72), indicating that samples with greater amounts of lower boiling constituents were more likely to be carcinogenic. The inverse relationship between boiling range and carcinogenicity was further demonstrated by fractionation of select RAE samples (MI=0.50+0.07; PAC=1.70+0.51wt%; n=5) into low and high boiling fractions, where lower boiling fractions were both more carcinogenic than the higher boiling fractions (MI=2.36±0.55 and 0.17±0.11, respectively) and enriched in 3-6 ring PACs (5.20+0.70wt% and 0.97+0.35wt%, respectively). The criteria defining carcinogenicity was established as 479°C for the 5% vaporization points by GCD, with an approximate 95% probability of a future sample having

  1. A cross-sectional study of a prototype carcinogenic human papillomavirus E6/E7 messenger RNA assay for detection of cervical precancer and cancer.

    Science.gov (United States)

    Castle, Philip E; Dockter, Janel; Giachetti, Cristina; Garcia, Francisco A R; McCormick, Mary Kay; Mitchell, Amy L; Holladay, E Blair; Kolk, Daniel P

    2007-05-01

    To evaluate carcinogenic human papillomavirus (HPV) mRNA for E6 and E7 mRNA detection on clinical specimens to identify women with cervical precancer and cancer. We evaluated a prototype assay that collectively detects oncogenes E6/E7 mRNA for 14 carcinogenic HPV genotypes on a sample of liquid cytology specimens (n=531), masked to clinical data and to the presence of HPV genotypes detected by PGMY09/11 L1 consensus primer PCR assay. We found an increasing likelihood of testing positive for carcinogenic HPV E6/E7 mRNA with increasing severity of cytology (P(Trend) E6/E7 mRNA. Overall, fewer specimens tested positive for carcinogenic HPV E6/E7 mRNA than for carcinogenic HPV DNA (PE6/E7 mRNA improved the association of positive test results with cervical precancer and cancer by reducing the number of test positives in women without precancer without reducing clinical sensitivity for cervical precancer and cancer compared with detection of carcinogenic HPV E6/E7 mRNA using a lower positive cutpoint by the same assay and with detection of carcinogenic HPV DNA. We found that carcinogenic HPV E6/E7 mRNA is a potentially useful biomarker for detection of cervical precancer and cancer and warrants further evaluation.

  2. Auditing laboratory rodent biosecurity programs.

    Science.gov (United States)

    Porter, William P; Horn, Mandy J; Cooper, Dale M; Klein, Hilton J

    2013-10-22

    A rodent biosecurity program that includes periodic evaluation of procedures used in an institution's vivarium can be used to ensure that best practices are in place to prevent a microbial pathogen outbreak. As a result of an ongoing comprehensive biosecurity review within their North American and European production facilities, the authors developed a novel biosecurity auditing process and worksheet that could be useful in other animal care and use operations. The authors encourage other institutions to consider initiating similar audits of their biosecurity programs to protect the health of their laboratory animals.

  3. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

    Farmer, P.B.; Sepai, O.; Lawrence, R.

    1996-01-01

    aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical......A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological...... for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers...

  4. Inhalation toxicity and carcinogenicity studies of cobalt sulfate.

    Science.gov (United States)

    Bucher, J R; Hailey, J R; Roycroft, J R; Haseman, J K; Sills, R C; Grumbein, S L; Mellick, P W; Chou, B J

    1999-05-01

    Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation

  5. Method for converting asbestos to non-carcinogenic compounds

    Science.gov (United States)

    Selby, Thomas W.

    1996-01-01

    Hazardous and carcinogenic asbestos waste characterized by a crystalline fibrous structure is transformed into non-carcinogenic, relatively nonhazardous, and non-crystalline solid compounds and gaseous compounds which have commercial utilization. The asbestos waste is so transformed by the complete fluorination of the crystalline fibrous silicate mineral defining the asbestos.

  6. Workshop on problem areas associated with developing carcinogen guidelines

    Energy Technology Data Exchange (ETDEWEB)

    1984-06-01

    A workshop was conducted to discuss problem areas associated with developing carcinogen guidelines. Session topics included (1) definition of a carcinogen for regulatory purposes; (2) potency; (3) risk assessment; (4) uncertainties; (5) de minimis quantity; and (6) legal and regulatory issues. Separate abstracts have been prepared for individual papers. (ACR)

  7. Incorporating potency into EU classification for carcinogenicity and reproductive toxicity.

    Science.gov (United States)

    Hennes, C; Batke, M; Bomann, W; Duhayon, S; Kosemund, K; Politano, V; Stinchcombe, S; Doe, J

    2014-11-01

    Although risk assessment, assessing the potential harm of each particular exposure of a substance, is desirable, it is not feasible in many situations. Risk assessment uses a process of hazard identification, hazard characterisation, and exposure assessment as its components. In the absence of risk assessment, the purpose of classification is to give broad guidance (through the label) on the suitability of a chemical in a range of use situations. Hazard classification in the EU is a process involving identification of the hazards of a substance, followed by comparison of those hazards (including degree of hazard) with defined criteria. Classification should therefore give guidance on degree of hazard as well as hazard identification. Potency is the most important indicator of degree of hazard and should therefore be included in classification. This is done for acute lethality and general toxicity by classifying on dose required to cause the effect. The classification in the EU for carcinogenicity and reproductive toxicity does not discriminate across the wide range of potencies seen (6 orders of magnitude) for carcinogenicity and for developmental toxicity and fertility. Therefore potency should be included in the classification process. The methodology in the EU guidelines for classification for deriving specific concentration limits is a rigorous process for assigning substances which cause tumours or developmental toxicity and infertility in experimental animals to high, medium or low degree of hazard categories by incorporating potency. Methods are suggested on how the degree of hazard so derived could be used in the EU classification process to improve hazard communication and in downstream risk management.

  8. Noncoding RNA response to xenobiotic exposure: an indicator of toxicity and carcinogenicity.

    Science.gov (United States)

    Marrone, April K; Beland, Frederick A; Pogribny, Igor P

    2014-10-01

    Human exposure to certain environmental and occupational chemicals is one of the major risk factors for noncommunicable diseases, including cancer. Therefore, it is desirable to take advantage of subtle exposure-related adverse cellular events for early disease detection and to identify potential dangers caused by new and currently under-evaluated drugs and chemicals. Nongenotoxic events due to carcinogen/toxicant exposure are a general hallmark of sustained cellular stress leading to tumorigenesis. These processes are globally regulated via noncoding RNAs (ncRNAs). Tumorigenesis-associated genotoxic and nongenotoxic events lead to the altered expression of ncRNAs and may provide a mechanistic link between chemical exposure and tumorigenesis. Current advances in toxicogenomics are beginning to provide valuable insight into gene-chemical interactions at the transcriptome level. In this review, we summarize recent information about the impact of xenobiotics on ncRNAs. Evidence highlighted in this review suggests a critical role of ncRNAs in response to carcinogen/toxicant exposure. Benefits for the use of ncRNAs in carcinogenicity assessment include remarkable tissue specificity, early appearance, low baseline variability, and their presence and stability in biological fluids, which suggests that the incorporation of ncRNAs in the evaluation of cancer risk assessment may enhance substantially the efficiency of toxicity and carcinogenicity testing.

  9. Emissions and air exposure of carcinogens and co-carcinogens in four Nordic countries

    DEFF Research Database (Denmark)

    Fauser, Patrik; Plejdrup, Marlene Schmidt; Ketzel, Matthias;

    . A list of carcinogenic andco-carcinogenic pollutants (particles, heavy metals and organic compounds) emittedfrom energy production, industrial activities, road transport, navigation, agriculture, residential heating and product use was compiled. Pollutant emissions levels for 2010and trends for 1990......This project (KoL 12-08) was performed for the Climate and Air Quality Group (KlimaogLuftgruppen, KoL), Nordic Council of Ministers by atmospheric emission, exposureand epidemiology experts from Denmark, Finland, Norway and Sweden. Emission inventory methods and exposure models were presented...... to 2010 were compiled and discussed, and modelled andmeasured atmospheric concentrations for 2010 were compiled on regional, urbanand local scales. Nordic maps of emissions and air concentrations of PM2.5, PM10, NOx,NMVOC, benzene, BaP, dioxin, cadmium and nickel were compiled for allaggregated main...

  10. Carcinogenic risk of copper gluconate evaluated by a rat medium-term liver carcinogenicity bioassay protocol

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Masayoshi; Usuda, Koji; Hayashi, Seigo; Ogawa, Izumi; Furukawa, Satoshi [Nissan Chemical Industries Limited, Toxicology and Environmental Science Department, Biological Research Laboratories, Saitama (Japan); Igarashi, Maki [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Nakae, Dai [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Tokyo Metropolitan Institute of Public Health, Tokyo (Japan)

    2008-08-15

    Carcinogenic risk and molecular mechanisms underlying the liver tumor-promoting activity of copper gluconate, an additive of functional foods, were investigated using a rat medium-term liver carcinogenicity bioassay protocol (Ito test) and a 2-week short-term administration experiment. In the medium-term liver bioassay, Fischer 344 male rats were given a single i.p. injection of N-nitrosodiethylamine at a dose of 200 mg/kg b.w. as a carcinogenic initiator. Starting 2 weeks thereafter, rats received 0, 10, 300 or 6,000 ppm of copper gluconate in diet for 6 weeks. All rats underwent 2/3 partial hepatectomy at the end of week 3, and all surviving rats were killed at the end of week 8. In the short-term experiment, rats were given 0, 10, 300 or 6,000 ppm of copper gluconate for 2 weeks. Numbers of glutathione S-transferase placental form (GST-P) positive lesions, single GST-P-positive hepatocytes and 8-oxoguanine-positive hepatocytes, and levels of cell proliferation and apoptosis in the liver were significantly increased by 6,000 ppm of copper gluconate in the medium-term liver bioassay. Furthermore, hepatic mRNA expression of genes relating to the metal metabolism, inflammation and apoptosis were elevated by 6,000 ppm of copper gluconate both in the medium-term liver bioassay and the short-term experiments. These results indicate that copper gluconate possesses carcinogenic risk toward the liver at the high dose level, and that oxidative stress and inflammatory and pro-apoptotic signaling statuses may participate in its underlying mechanisms. (orig.)

  11. Urban resident attitudes toward rodents, rodent control products, and environmental effects

    Science.gov (United States)

    Rodent control in urban areas can result in the inadvertent mortality of non-target species (e.g., bobcats). However, there is little detailed information about rodent control practices of urban residents. Our objective was to evaluate urban rodent control behaviors in two area...

  12. Urban resident attitudes toward rodents, rodent control products, and environmental effects

    Science.gov (United States)

    Rodent control in urban areas can result in the inadvertent mortality of non-target species (e.g., bobcats). However, there is little detailed information about rodent control practices of urban residents. Our objective was to evaluate urban rodent control behaviors in two area...

  13. Chemoprevention by grape seed extract and genistein in carcinogen-induced mammary cancer in rats is diet dependent.

    Science.gov (United States)

    Kim, Helen; Hall, Patti; Smith, Michelle; Kirk, Marion; Prasain, Jeevan K; Barnes, Stephen; Grubbs, Clinton

    2004-12-01

    Many popular dietary supplements are enriched in polyphenols such as the soy isoflavones, tea catechins, and resveratrol (from grape skins), each of which has been shown to have chemopreventive activity in cellular models of cancer. The proanthocyanidins, which are oligomers of the catechins, are enriched in grape seeds and form the basis of the dietary supplement grape seed extract (GSE). Evidence suggests that the proanthocyanidins may be metabolized to the monomeric catechins. This study was carried out to determine whether GSE added to rodent diets protected against carcinogen-induced mammary tumorigenesis in rats and whether this was affected by the composition of the whole diet. Female rats were begun on 5%, 1.25%, or 0% (control) GSE-supplemented diets at age 35 d. At age 50 d they were administered 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil at 80 mg/kg body weight. They were weighed and monitored weekly for tumor development until 120 d after DMBA administration. Administration of GSE in AIN-76A diet did not show any protective activity of GSE against DMBA-induced breast cancer. However, administration of GSE in a laboratory dry food diet (Teklad 4% rodent diet) resulted in a 50% reduction in tumor multiplicity. In similar experiments, genistein administered in AIN-76A diet also failed to show chemopreventive activity against the carcinogen N-methyl-N-nitrosourea; however, when administered at the same dose in the Teklad 4% rodent diet, genistein exhibited significant chemopreventive activity (44-61%). These results demonstrate that GSE is chemopreventive in an animal model of breast cancer; moreover, the diet dependency of the chemopreventive activity for both GSE and genistein suggests that whether or not a compound is chemopreventive may depend on the diet in which the agent is administered.

  14. Lassa serology in natural populations of rodents and horizontal transmission.

    Science.gov (United States)

    Fichet-Calvet, Elisabeth; Becker-Ziaja, Beate; Koivogui, Lamine; Günther, Stephan

    2014-09-01

    Lassa virus causes hemorrhagic fever in West Africa. Previously, we demonstrated by PCR screening that only the multimammate mouse, Mastomys natalensis, hosts Lassa virus in Guinea. In the present study, we used the same specimen collection from 17 villages in Coastal, Upper, and Forest Guinea to investigate the Lassa virus serology in the rodent population. The aim was to determine the dynamics of antibody development in M. natalensis and to detect potential spillover infections in other rodent species. Immunoglobulin G (IgG) antibody screening was performed using the indirect immunofluorescence assay with the Guinean Lassa virus strain Bantou 289 as antigen. The overall seroprevalence was 8% (129/1551) with the following rodents testing positive: 109 M. natalensis, seven Mastomys erythroleucus, four Lemniscomys striatus, four Praomys daltoni, three Mus minutoides, and two Praomys rostratus. Nearly all of them (122/129) originated from Bantou, Tanganya, and Gbetaya, where Lassa virus is highly endemic in M. natalensis. The antibody seroprevalence in M. natalensis from this high-endemic area (27%; 108/396) depended on the village, habitat, host age, and host abundance. A main positive factor was age; the maximum seroprevalence reached 50% in older animals. Our data fit with a model implicating that most M. natalensis rodents become horizontally infected, clear the virus within a period significantly shorter than their life span, and develop antibodies. In addition, the detection of antibodies in other species trapped in the habitats of M. natalensis suggests spillover infections.

  15. Protozoan Parasites of Rodents and Their Zoonotic Significance in Boyer-Ahmad District, Southwestern Iran.

    Science.gov (United States)

    Seifollahi, Zeinab; Sarkari, Bahador; Motazedian, Mohammad Hossein; Asgari, Qasem; Ranjbar, Mohammad Javad; Abdolahi Khabisi, Samaneh

    2016-01-01

    Backgrounds. Wild rodents are reservoirs of various zoonotic diseases, such as toxoplasmosis, babesiosis, and leishmaniasis. The current study aimed to assess the protozoan infection of rodents in Boyer-Ahmad district, southwestern Iran. Materials and Methods. A total of 52 rodents were collected from different parts of Boyer-Ahmad district, in Kohgiluyeh and Boyer-Ahmad province, using Sherman live traps. Each rodent was anesthetized with ether, according to the ethics of working with animals, and was dissected. Samples were taken from various tissues and stool samples were collected from the contents of the colon and small intestines. Moreover, 2 to 5 mL of blood was taken from each of the rodents and the sera were examined for anti-Leishmania antibodies, by ELISA, or anti-T. gondii antibodies, by modified agglutination test (MAT). DNA was extracted from brain tissue samples of each rodent and PCR was used to identify the DNA of T. gondii. Results. Of the 52 stool samples of rodents studied by parasitological methods, intestinal protozoa infection was seen in 28 cases (53.8%). From 52 rodents, 19 (36.5%) were infected with Trichomonas, 10 (19.2%) with Giardia muris, and 11 (21.2%) with Entamoeba spp. Also, 10 cases (19.2%) were infected with Blastocystis, 3 (5.8%) were infected with Chilomastix, 7 (13.5%) were infected with Endolimax, 1 (1.9%) was infected with Retortamonas, 3 (5.77%) were infected with T. gondii, and 6 (11.54%) were infected with Trypanosoma lewisi. Antibodies to T. gondii were detected in the sera of 5 (9.61%) cases. Results of the molecular study showed T. gondii infection in 3 (5.77%) of the rodents. Findings of this study showed that rodents in Kohgiluyeh and Boyer-Ahmad province, southwestern Iran, are infected with several blood and intestinal parasites; some of them might be potential risks to residents and domestic animals in the region.

  16. Use of in vivo/in vitro unscheduled DNA synthesis for identification of organ-specific carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Furihata, C.; Matsushima, T.

    1987-01-01

    There are still only a few in vivo short-term assay methods for predicting potential organ-specific carcinogens and mutagens in mammals, although such methods are required for evaluating the in vivo effects of in vitro mutagens. In the in vivo/in vitro UDS assay methods described here, chemicals are given to experimental animals and induction of UDS in target organs is determined by in vitro organ culture or primary cell culture in the presence of (/sup 3/H)dThd. Incorporation of (/sup 3/H)dThd into DNA is measured with a liquid scintillation counter or by autoradiography. These methods have now been applied to the glandular stomach, forestomach, colon, liver, kidney, pancreas, tracheal epithelium, nasal epithelium, and spermatocytes. With minor modifications, they may also be applied to other organs. The present review shows that induction of UDS in various organs correlated well with the induction of cancer in these organs. The present authors have used the present methods to identify some potential organ-specific mutagens and carcinogens in mammals. The present authors found that three dicarbonyl compounds, glyoxal, methylglyoxal, and diacetyl, induced apparent UDS and TDS in the glandular stomach, and other groups found that 2-NT, MA6BT, and CNEt6BT induced UDS in the liver. These in vivo/in vitro UDS assays are better than in vitro UDS assay for identification of potential organ-specific mutagens and carcinogens in mammals and are especially useful for identifying potential mutagens and carcinogens that are specific for certain organs, such as the stomach, liver, and kidney. They are also useful for examining the potential mutagenicities and carcinogenicities of carcinogen analogs. However, these methods are not suitable for general in vivo screening because they are not yet available for all organs. 113 references.

  17. Besnoitiosis in rodents from Colorado. [Parasitic infestations

    Energy Technology Data Exchange (ETDEWEB)

    Dagle, G E; Winsor, T F; Adee, R R

    1976-01-01

    Parasitic cysts of Besnoitia jellisoni (coccidia) were found in rodents (Peromyscus maniculatus and Spermophilus tridecemlineatus) trapped in Eastern Colorado. The parasite was associated with a granulomatous inflammatory reaction in the lungs of each rodent and was disseminated in several organs from one Peromyscus. The ultrastructural appearance of the merozoites and the cyst wall formed by the host cell were studied.

  18. CORAL software: prediction of carcinogenicity of drugs by means of the Monte Carlo method.

    Science.gov (United States)

    Toropova, Alla P; Toropov, Andrey A

    2014-02-14

    Methodology of building up and validation of models for carcinogenic potentials of drugs by means of the CORAL software is described. The QSAR analysis by the CORAL software includes three phases: (i) definition of preferable parameters for the optimization procedure that gives maximal correlation coefficient between endpoint and an optimal descriptor that is calculated with so-called correlation weights of various molecular features; (ii) detection of molecular features with stable positive correlation weights or vice versa stable negative correlation weights (molecular features which are characterized by solely positive or solely negative correlation weights obtained for several starts of the Monte Carlo optimization are a basis for mechanistic interpretations of the model); and (iii) building up the model that is satisfactory from point of view of reliable probabilistic criteria and OECD principles. The methodology is demonstrated for the case of carcinogenicity of a large set (n = 1464) of organic compounds which are potential or actual pharmaceutical agents.

  19. Bartonella species in invasive rats and indigenous rodents from Uganda.

    Science.gov (United States)

    Billeter, Sarah A; Borchert, Jeff N; Atiku, Linda A; Mpanga, Joseph T; Gage, Kenneth L; Kosoy, Michael Y

    2014-03-01

    The presence of bartonellae in invasive rats (Rattus rattus) and indigenous rodents (Arvicanthis niloticus and Cricetomys gambianus) from two districts in Uganda, Arua and Zombo, was examined by PCR detection and culture. Blood from a total of 228 R. rattus, 31 A. niloticus, and 5 C. gambianus was screened using genus-specific primers targeting the 16S-23S intergenic spacer region. Furthermore, rodent blood was plated on brain heart infusion blood agar, and isolates were verified as Bartonella species using citrate synthase gene- (gltA) specific primers. One hundred and four fleas recovered from R. rattus were also tested for the presence of Bartonella species using the same gltA primer set. An overall prevalence of 1.3% (three of 228) was obtained in R. rattus, whereas 61.3% of 31 A. niloticus and 60% of five C. gambianus were positive for the presence of Bartonella species. Genotypes related to Bartonella elizabethae, a known zoonotic pathogen, were detected in three R. rattus and one C. gambianus. Bartonella strains, similar to bacteria detected in indigenous rodents from other African countries, were isolated from the blood of A. niloticus. Bartonellae, similar to bacteria initially cultured from Ornithodorus sonrai (soft tick) from Senegal, were found in two C. gambianus. Interestingly, bartonellae detected in fleas from invasive rats were similar to bacteria identified in indigenous rodents and not their rat hosts, with an overall prevalence of 6.7%. These results suggest that if fleas are competent vectors of these bartonellae, humans residing in these two districts of Uganda are potentially at greater risk for exposure to Bartonella species from native rodents than from invasive rats. The low prevalence of bartonellae in R. rattus was quite surprising, in contrast, to the detection of these organisms in a large percentage of Rattus species from other geographical areas. A possible reason for this disparity is discussed.

  20. Barnes maze testing strategies with small and large rodent models.

    Science.gov (United States)

    Rosenfeld, Cheryl S; Ferguson, Sherry A

    2014-02-26

    Spatial learning and memory of laboratory rodents is often assessed via navigational ability in mazes, most popular of which are the water and dry-land (Barnes) mazes. Improved performance over sessions or trials is thought to reflect learning and memory of the escape cage/platform location. Considered less stressful than water mazes, the Barnes maze is a relatively simple design of a circular platform top with several holes equally spaced around the perimeter edge. All but one of the holes are false-bottomed or blind-ending, while one leads to an escape cage. Mildly aversive stimuli (e.g. bright overhead lights) provide motivation to locate the escape cage. Latency to locate the escape cage can be measured during the session; however, additional endpoints typically require video recording. From those video recordings, use of automated tracking software can generate a variety of endpoints that are similar to those produced in water mazes (e.g. distance traveled, velocity/speed, time spent in the correct quadrant, time spent moving/resting, and confirmation of latency). Type of search strategy (i.e. random, serial, or direct) can be categorized as well. Barnes maze construction and testing methodologies can differ for small rodents, such as mice, and large rodents, such as rats. For example, while extra-maze cues are effective for rats, smaller wild rodents may require intra-maze cues with a visual barrier around the maze. Appropriate stimuli must be identified which motivate the rodent to locate the escape cage. Both Barnes and water mazes can be time consuming as 4-7 test trials are typically required to detect improved learning and memory performance (e.g. shorter latencies or path lengths to locate the escape platform or cage) and/or differences between experimental groups. Even so, the Barnes maze is a widely employed behavioral assessment measuring spatial navigational abilities and their potential disruption by genetic, neurobehavioral manipulations, or drug

  1. Monitoring rodents movements with a biomarker around introduction and feeding foci in an urban environment in Tanzania

    DEFF Research Database (Denmark)

    Mohr, Katrine; Leirs, Herwig; Katakweba, Abdul

    2007-01-01

    , Rhodamine B (RB), we investigated the distances over which rodents are active around such potential introduction sites. Animals feeding at such sites were traced up to 100 m distant within a period of 10 days.We found that RB is a practical alternative for studying rodent movements. These results may be...

  2. Bioindication of mutagenic and carcinogenic pollutants in waters of the Oława River.

    Science.gov (United States)

    Pawlaczyk-Szpilowa, M; Sztajer, H; Traczewska, T

    1985-01-01

    Samples of raw waters from the Oława River, chlorinated raw water, raw water filtered through activated charcoal and treated and chlorinated water before and after ozonization were examined with the use of the Ames test for potential carcinogenic activity. Positive results were obtained for raw water with Salmonella typhimurium strains TA 98 and TA 1535 and for chlorinated raw water with strain TA 1537.

  3. Relationship between Structures and Carcinogenicities of Heterocyclic Amines

    Institute of Scientific and Technical Information of China (English)

    JU Xue-hai; DAI Qian-huan; CHEN Sha; WANG Wen-jun

    2004-01-01

    Semi-empirical molecular orbital calculations were performed on heterocyclic aromatic amines(HCAs). The relationship between the structures and the carcinogenicities can be rationally elucidated by the models based on the metabolism of HCAs and the Di-region theory. The degree of easiness for the formation of Di-region electrophilic centers determines the carcinogenic activity. There is a good linear relationship between the observed carcinogenicities and the PM3 calculated parameters, with r=0.973 and F=29.8>(F*0.*01).

  4. A STUDY ON RODENT ECTOPARASITES IN BANDAR ABBAS: THE MAIN ECONOMIC SOUTHERN SEAPORT OF IRAN

    Directory of Open Access Journals (Sweden)

    A. A. Hanafi-Bojd, M. Shahi, M. Baghaii, M. Shayeghi, N. Razmand, A. Pakari

    2007-07-01

    Full Text Available Rodents are one of the main health problems in the cities, especially in coastal area. These animals make economic damages and are potential health dangers in Bandar Abbas, the main economic southern port of Iran. In this study, rodents were captured from different parts of the city, before and after a control program during 2003-2004, transferred to the laboratory, identified and examined for ecto-parasites. Totally 105 rodents demonstrating four species: Rattus rattus (3%, R. norvegicus (78%, Mus musculus (3% and Tatera indica (16%, were captured before the control program. The most frequency was observed in Ayatollah Ghafari quarter, 10 rodents per 24 traps. After 12 months, the duration of control program, rodents were re-captured to assessment the success of control activity. In this stage 35 small mammals demonstrated four species were obtained: R.norvegicus (51.4%, R.rattus (37.1%, T.indica (8.6% and one weasel (2.9%. We found the most frequency in Khoon-sorkh quarter with 6 rodents per 24 traps. The identified ectoparasites were Xenopsylla buxtoni, Rhipicephalus sp., Polyplax gerbilli, Haplopleura captiosa, Ornithonyssus bacoti, Laelaps nuttalli, Dermanyssus americanus, Dermanyssus sanguineus, Haemolaelaps glasgowi and Echinolaelaps echidninus. The number of rodents reduced to one third after control program, shows the relative success of this program (p<0.05.

  5. Hematological profile as a crude oil exposure-related marker in wild rodents

    Directory of Open Access Journals (Sweden)

    Ana L. Muccillo-Baisch

    2013-01-01

    Full Text Available The toxicity of petroleum components is well described in the literature, especially with regard to mutagenic and carcinogenic effects. In some groups of animals, such as birds, oil exposure seems to alter blood parameters, while this relationship is poorly understood in rodents. The study aimed to investigate alterations in hematological profile in the wild rodent Calomys laucha exposed to crude oil contaminated soils. In this study, males specimens of Calomys laucha were exposed for 14 days to two soils contaminated by petroleum: (I landfarming soil, coming from a bioremediation area of contaminated soil from a Petrochemical Complex through landfarming technique and (II soil of a simulated oil spill in laboratory conditions. The animals were exposed individually in cages containing 1 kg soil with free access to food and water. Control animals were exposed to an artificial uncontaminated soil. At the end of the experiment, animals were anesthetized and blood was collected for hematological profile. The animals exposed to soil landfarming had significant reduction in the number of bands, segmented, eosinophils, monocytes, lymphocytes and increased red cell distribution width (RDW, while animals exposed to simulated soil spillage in laboratory had decreased number of bands, but an increase in the number of lymphocytes and platelets. These changes in hemostasis may indicate an early stage of the development of associated pathologies, while the hematological profile can be used as a crude oil exposure-related marker in wild rodents.

  6. Epidemiological distribution of rodents as potent reservoirs for infectious diseases in the provinces of Mazandaran, Gilan and Golestan, northern Iran

    Directory of Open Access Journals (Sweden)

    Behzad Esfandiari

    2017-05-01

    Full Text Available Rodents are mammals that comprise more than 2000 species and approximately 30 families. There are many morphological and ecological differences among them as variations in their shape, size, weight and habitat. In addition to significant economic losses, rodents have a major role in the dissemination of infectious diseases caused by viruses, bacteria, parasites or other micro-organisms. Rodents are important reservoirs of diseases which have been observed in many cities of Iran provinces especially along Caspian Sea border to Alborz Mountain. The aim of this study is to assess the geographical distribution of rodents in three provinces of northern part of Iran as reservoir of potential endemic infectious diseases. Rodents in 10 major parts of each of the three provinces of Mazandaran, Gilan and Golestan, northern Iran were collected and a total of 404 rodents were trapped alive. They were determined by the key characteristics such as gender, genus, species, different locations and topological situation. Statistical analysis was performed to characterize the study sample and to correlate all variables and parameters. The distribution frequencies of three, five and six genera of rodents were identified in Mazandaran, Gilan and Golestan provinces respectively. The overall distribution frequency of eight genera of rodents in the three provinces were identified as Rattus (R. norvegicus (67.3%, R. rattus (13.6%, Apodemus sylvaticus (13.9%, Arvicola (1%, Mus musculus (0.3%, Nesokia indica (2.5%, Cricetulus migrates (0.7% and Rhombomys opimus (0.7%. The results of this study determined the geographic distribution of the rodents in the three northern provinces of Iran. It is indicated the association of various distribution and diversity of rodents with provincial location. The overall distribution frequency of eight genera of rodents was recognized in the above three provinces geographical locations. This study confirms epidemiological distribution of

  7. Wild Rodent Ectoparasites Collected from Northwestern Iran

    Directory of Open Access Journals (Sweden)

    Zabihollah Zarei

    2017-04-01

    Full Text Available Background: Rodents play an important role as reservoir of some pathogens, and the host of some ectoparasites as well. These ectoparasites can transmit rodents’ pathogens to human or animals. The aim of this study was to assess the distribution and infestation load of ectoparasites on rodents in Meshkin-Shahr District, northwestern Iran.Method: Rodents were captured using baited live traps in spring 2014 from Meshkin-Shahr District and were trans­ferred to the laboratory for identification to the species level. Their ectoparasites were collected, mounted and identi­fied.Results: Three rodent species including Meriones persicus (74%, Mus musculus (16.9% and Cricetulus migrato­rius (9% were identified. Among all rodents, 185 specimens (90.69% were infested with a total of 521 ectopara­sites. Overall, 10 arthropods species were collected, including fleas (97.6%, one mite (1.6% and one louse species (0.6% as follows: Xenopsylla nubica, X. astia, X. buxtoni, X. cheopis, Nosopsyllus fasciatus, N. iranus, Cten­ocephalides felis, Ctenophthalmus rettigismiti, Ornithonyssus sp and one species of genus Polyplax. The most prev­alent ectoparasites species was X. nubica (89%.Conclusion: Nearly all rodent species were infested with Xenopsylla species. Monitoring of ectoparasites on infested rodents is very important for awareness and early warning towards control of arthropod-borne diseases.

  8. Correlates of Recent Declines of Rodents in Northern and Southern Australia: Habitat Structure Is Critical.

    Directory of Open Access Journals (Sweden)

    Michael J Lawes

    Full Text Available Australia has experienced dramatic declines and extinctions of its native rodent species over the last 200 years, particularly in southern Australia. In the tropical savanna of northern Australia significant declines have occurred only in recent decades. The later onset of these declines suggests that the causes may differ from earlier declines in the south. We examine potential regional effects (northern versus southern Australia on biological and ecological correlates of range decline in Australian rodents. We demonstrate that rodent declines have been greater in the south than in the tropical north, are strongly influenced by phylogeny, and are consistently greater for species inhabiting relatively open or sparsely vegetated habitat. Unlike in marsupials, where some species have much larger body size than rodents, body mass was not an important predictor of decline in rodents. All Australian rodent species are within the prey-size range of cats (throughout the continent and red foxes (in the south. Contrary to the hypothesis that mammal declines are related directly to ecosystem productivity (annual rainfall, our results are consistent with the hypothesis that disturbances such as fire and grazing, which occur in non-rainforest habitats and remove cover used by rodents for shelter, nesting and foraging, increase predation risk. We agree with calls to introduce conservation management that limits the size and intensity of fires, increases fire patchiness and reduces grazing impacts at ecological scales appropriate for rodents. Controlling feral predators, even creating predator-free reserves in relatively sparsely-vegetated habitats, is urgently required to ensure the survival of rodent species, particularly in northern Australia where declines are not yet as severe as those in the south.

  9. Detection of Leishmania donovani and L. tropica in Ethiopian wild rodents.

    Science.gov (United States)

    Kassahun, Aysheshm; Sadlova, Jovana; Dvorak, Vit; Kostalova, Tatiana; Rohousova, Iva; Frynta, Daniel; Aghova, Tatiana; Yasur-Landau, Daniel; Lemma, Wessenseged; Hailu, Asrat; Baneth, Gad; Warburg, Alon; Volf, Petr; Votypka, Jan

    2015-05-01

    Human visceral (VL, also known as Kala-azar) and cutaneous (CL) leishmaniasis are important infectious diseases affecting countries in East Africa that remain endemic in several regions of Ethiopia. The transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various Leishmania spp., sand fly vectors, and reservoir animals besides human hosts. Particularly in East Africa, the role of animals as reservoirs for human VL remains unclear. Isolation of Leishmania donovani parasites from naturally infected rodents has been reported in several endemic countries; however, the status of rodents as reservoirs in Ethiopia remains unclear. Here, we demonstrated natural Leishmania infections in rodents. Animals were trapped in 41 localities of endemic and non-endemic areas in eight geographical regions of Ethiopia and DNA was isolated from spleens of 586 rodents belonging to 21 genera and 38 species. Leishmania infection was evaluated by real-time PCR of kinetoplast (k)DNA and confirmed by sequencing of the PCR products. Subsequently, parasite species identification was confirmed by PCR and DNA sequencing of the 18S ribosomal RNA internal transcribed spacer one (ITS1) gene. Out of fifty (8.2%) rodent specimens positive for Leishmania kDNA-PCR and sequencing, 10 were subsequently identified by sequencing of the ITS1 showing that five belonged to the L. donovani complex and five to L. tropica. Forty nine kDNA-positive rodents were found in the endemic localities of southern and eastern Ethiopia while only one was identified from northwestern Ethiopia. Moreover, all the ten ITS1-positive rodents were captured in areas where human leishmaniasis cases have been reported and potential sand fly vectors occur. Our findings suggest the eco-epidemiological importance of rodents in these foci of leishmaniasis and indicate that rodents are likely to play a role in the transmission of leishmaniasis in Ethiopia

  10. Correlates of Recent Declines of Rodents in Northern and Southern Australia: Habitat Structure Is Critical.

    Science.gov (United States)

    Lawes, Michael J; Fisher, Diana O; Johnson, Chris N; Blomberg, Simon P; Frank, Anke S K; Fritz, Susanne A; McCallum, Hamish; VanDerWal, Jeremy; Abbott, Brett N; Legge, Sarah; Letnic, Mike; Thomas, Colette R; Thurgate, Nikki; Fisher, Alaric; Gordon, Iain J; Kutt, Alex

    2015-01-01

    Australia has experienced dramatic declines and extinctions of its native rodent species over the last 200 years, particularly in southern Australia. In the tropical savanna of northern Australia significant declines have occurred only in recent decades. The later onset of these declines suggests that the causes may differ from earlier declines in the south. We examine potential regional effects (northern versus southern Australia) on biological and ecological correlates of range decline in Australian rodents. We demonstrate that rodent declines have been greater in the south than in the tropical north, are strongly influenced by phylogeny, and are consistently greater for species inhabiting relatively open or sparsely vegetated habitat. Unlike in marsupials, where some species have much larger body size than rodents, body mass was not an important predictor of decline in rodents. All Australian rodent species are within the prey-size range of cats (throughout the continent) and red foxes (in the south). Contrary to the hypothesis that mammal declines are related directly to ecosystem productivity (annual rainfall), our results are consistent with the hypothesis that disturbances such as fire and grazing, which occur in non-rainforest habitats and remove cover used by rodents for shelter, nesting and foraging, increase predation risk. We agree with calls to introduce conservation management that limits the size and intensity of fires, increases fire patchiness and reduces grazing impacts at ecological scales appropriate for rodents. Controlling feral predators, even creating predator-free reserves in relatively sparsely-vegetated habitats, is urgently required to ensure the survival of rodent species, particularly in northern Australia where declines are not yet as severe as those in the south.

  11. Multiplex PCR identification of Taenia spp. in rodents and carnivores.

    Science.gov (United States)

    Al-Sabi, Mohammad N S; Kapel, Christian M O

    2011-11-01

    The genus Taenia includes several species of veterinary and public health importance, but diagnosis of the etiological agent in definitive and intermediate hosts often relies on labor intensive and few specific morphometric criteria, especially in immature worms and underdeveloped metacestodes. In the present study, a multiplex PCR, based on five primers targeting the 18S rDNA and ITS2 sequences, produced a species-specific banding patterns for a range of Taenia spp. Species typing by the multiplex PCR was compared to morphological identification and sequencing of cox1 and/or 12S rDNA genes. As compared to sequencing, the multiplex PCR identified 31 of 32 Taenia metacestodes from rodents, whereas only 14 cysts were specifically identified by morphology. Likewise, the multiplex PCR identified 108 of 130 adult worms, while only 57 were identified to species by morphology. The tested multiplex PCR system may potentially be used for studies of Taenia spp. transmitted between rodents and carnivores.

  12. Environmental carcinogens and mutational pathways in atherosclerosis.

    Science.gov (United States)

    Pulliero, A; Godschalk, R; Andreassi, M G; Curfs, D; Van Schooten, F J; Izzotti, A

    2015-05-01

    Atherosclerosis is associated with DNA damage in both circulating and vessel-wall cells and DNA adducts derived from exposure to environmental mutagens are abundant in atherosclerotic vessels. Environmental chemical carcinogens identified as risk factor for atherosclerosis include polycyclic aromatic hydrocarbons (benzo(a)pyrene, dimethylbenz(a)anthracene, beta-naphthoflavone, pyrene, 3-methylcolanthrene), arsenic, cadmium, 1,3-butadiene, cigarette smoke. Accordingly, polymorphisms of genes encoding for phase I/II metabolic reaction and DNA repair are risk factor for cardiovascular diseases, although their role is negligible as compared to other risk factors. The pathogenic relevance of mutation-related molecular damage in atherosclerosis has been demonstrated in experimental animal models involving the exposure to chemical mutagens. The relevance of mutation-related events in worsening atherosclerosis prognosis has been demonstrated in human clinical studies mainly as referred to mitochondrial DNA damage. Atherosclerosis is characterized by the occurrence of high level of oxidative damage in blood vessel resulting from both endogenous and exogenous sources. Mitochondrial damage is a main endogenous source of oxidative stress whose accumulation causes activation of intrinsic apoptosis through BIRC2 inhibition and cell loss contributing to plaque development and instability. Environmental physical mutagens, including ionizing radiation, are a risk factor for atherosclerosis even at the low exposure dose occurring in case of occupational exposure or the high exposure doses occurring during radiotherapy. Conversely, the role of exciting UV radiation in atherosclerosis is still uncertain. This review summarizes the experimental and clinical evidence supporting the pathogenic role of mutation-related pathway in atherosclerosis examining the underlying molecular mechanisms.

  13. The Applicability of a Short-term Test for Detection of Modifying Effects of Dietary Factors in Rodent Colon Carcinogenesis

    DEFF Research Database (Denmark)

    Kristiansen, Eva

    HCl or AOM for their modulating effect on the development of aberrant crypt foci (ACF). Furthermore the heterocyclic amines IQ and PhIP were introduced in the assay as inducers of ACF in mice and rats and their role in colon carcinogenesis in mice was investigated. ACF were found to be induced...... in rodent colon by the colon carcinogens DMH-2HC1, AOM, IQ, and PhIP and it was shown that the incidence of the induced ACF could be modulated by dietary components such as sucrose, dietary fibre, and starch....

  14. A compilation of genotoxicity and carcinogenicity data on aromatic aminosulphonic acids.

    Science.gov (United States)

    Jung, R; Steinle, D; Anliker, R

    1992-07-01

    A review is presented to evaluate existing information on genotoxicity and carcinogenicity testing of various aromatic aminosulphonic acids (AASAs). A great variety of water-soluble azo dyes can form aromatic phenyl- or naphthyl-aminosulphonic acids by chemical and enzymatic reduction. AASAs are also used as intermediates in the synthesis of azo dyes and azo pigments and can arise as contaminants in the final products. Comparisons have been made with the data available on the corresponding unsulphonated analogues, some of which are known to be genotoxic and/or carcinogenic. The vast majority of the AASAs were conclusively non-mutagenic in the Ames test. In most cases the absence of genotoxicity was also demonstrated with a variety of other test systems in vitro and in vivo. It is concluded that AASAs, in contrast with some of their unsulphonated analogues, generally have no or very low genotoxic and tumorigenic potential.

  15. Carcinogenic risk assessment for emissions from clinical waste incineration and road traffic.

    Science.gov (United States)

    Wheatley, Andrew; Sadhra, Steven

    2010-10-01

    The most significant potentially carcinogenic substances arising from a state-of-the-art clinical waste incinerator (CWI) and vehicle emissions were identified as polychlorinated dibenzo-p-dioxins, polycyclic aromatic hydrocarbons (PAHs), benzene, 1-butadiene, arsenic, cadmium, chromium and nickel. Long-term exposures of the notional maximum exposed individual (MEI) in the local environment, together with aggregate emissions from transport of clinical waste, were estimated. Mass emission rates of PAHs from the CWI to air were compared with previously published estimates of mass emissions to land from CWI bottom ash. Aggregate emissions from road transport of clinical waste were of a similar order to stack emissions from incineration. Mass emissions of PAHs to landfill generally greatly exceeded those from stack emissions. Emissions associated with operation of the CWI present a negligible contribution to overall cancer risk from PAHs and other carcinogens. Uncertainty in the quantitative risk estimates presented here is discussed in the context of these findings.

  16. Does the term carcinogen send the wrong message?

    Science.gov (United States)

    Flamm, W G; Hughes, D

    1997-08-19

    The term carcinogen has been used by scientists and health regulatory officials for decades. During the last 20 years there have been attempts to redefine the term to make it more rigorous. But, as predicted two decades ago by a benchmark-setting subcommittee of the National Cancer Advisory Board, advances in scientific understanding have brought about dramatic changes in the way we are able to view the term carcinogen. These changes, their scientific bases and their effect on defining the term carcinogen are described. An alternative to the use of the term carcinogen is suggested by the recently proposed US Environmental Agency's guidelines for cancer risk assessment which appear to be in accord with current scientific understanding and the importance of considering the factors affecting the term carcinogen. The guidelines set forth four questions, the answers to which could, in our judgment, replace the need to define or use the term carcinogen which, in light of new scientific knowledge, has become more misleading than useful.

  17. Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard

    Science.gov (United States)

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2013-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

  18. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

    Science.gov (United States)

    Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.

  19. Chronic Dermal Toxicity of Epoxy Resins I. Skin Carcinogenic Potency and General Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Holland, J.M.

    2001-01-16

    Epoxy resins are a diverse class of chemicals that differ in structure, physical properties, and, presumably, biological activity. The purpose of these experiments was to compare the chronic dermal toxicity and carcinogenicity of selected commercial epoxy resins and to determine the potential for positive synergistic carcinogenic interactions between different resins. This work is an extension and continuation of a Department of Energy sponsored program to evaluate epoxy resins for potential occupational health risks. The materials examined were chosen on the basis of their interest to the U.S. government. They are representative of the manufacturer's production at the time, and therefore the data are completely valid only for the specific production period. Results of the experimental exposures will be reported in two parts. This report describes the test materials, their chemical and physical characteristics and the experimental design. General (systemic) toxicity will be evaluated and the skin carcinogenicity of the materials compared. A subsequent report will provide morphological descriptions of skin and significant internal pathology induced by the various treatments.

  20. Assessment of the Effects of Acute and Repeated Exposure to Blast Overpressure in Rodents: Towards a Greater Understanding of Blast and the Potential Ramifications for Injury in Humans Exposed to Blast

    Directory of Open Access Journals (Sweden)

    Stephen Thomas Ahlers

    2012-03-01

    Full Text Available Mild traumatic brain injury (mTBI resulting from exposure to improvised explosive devices (IEDs has fueled a requirement to develop animals models that mirror this condition using exposure to blast overpressure (BOP. En route to developing a model of repeated exposure to BOP we sought to initially characterize the effects of acute BOP exposure in rodents, focusing specifically on the levels of BOP exposure that produced clinical mTBI symptoms. We first measured BOP effects on gross motor function on a balance beam. Separate groups of unanesthetized rats were exposed (in different orientations to 40 kPa, 75 kPa and 120 kPa BOP exposure inside a pneumatically driven shock tube. Results demonstrated that rats exposed to 120 kPa demonstrated transient alterations or loss of consciousness indicated by a transient loss of righting and by increased latencies on the balance beam. The 120 kPa exposure was the threshold for overt pathology for acute BOP exposure with approximately 30% of rats presenting with evidence of subdural hemorrhage and cortical contusions. All animals exposed to 120 kPa BOP manifested evidence of significant pulmonary hemorrhage. Anterograde memory deficits were observed in rats exposed to 75 kPa facing the BOP wave and rats exposed to 120 kPa in the lateral (side orientation. We next assessed repeated exposure to either lateral or frontal 40 kPa BOP in anesthetized rats, once per day for 12 days. Results showed that repeated exposure in the frontal, but not side, orientation to the BOP wave produced a transitory learning deficit on a Morris water maze (MWM task as shown by significantly longer latencies to reach the submerged platform in the second and third blocks of a four block session. Implications of these data are discussed in relation to the manifestation of mTBI in military personnel exposed to IEDs. Finally, we suggest that there are multiple types of brain injury from blast.

  1. Carcinogenicity and genotoxicity of ethylene oxide: new aspects and recent advances.

    Science.gov (United States)

    Thier, R; Bolt, H M

    2000-09-01

    Long-term inhalation studies in rodents have presented unequivocal evidence of experimental carcinogenicity of ethylene oxide, based on the formation of malignant tumors at multiple sites. However, despite a considerable body of epidemiological data only limited evidence has been obtained of its carcinogenicity in humans. Ethylene oxide is not only an important exogenous toxicant, but it is also formed from ethylene as a biological precursor. Ethylene is a normal body constituent; its endogenous formation is evidenced by exhalation in rats and in humans. Consequently, ethylene oxide must also be regarded as a physiological compound. The most abundant DNA adduct of ethylene oxide is 7-(2-hydroxyethyl)guanine (HOEtG). Open questions are the nature and role of tissue-specific factors in ethylene oxide carcinogenesis and the physiological and quantitative role of DNA repair mechanisms. The detection of remarkable individual differences in the susceptibility of humans has promoted research into genetic factors that influence the metabolism of ethylene oxide. With this background it appears that current PBPK models for trans-species extrapolation of ethylene oxide toxicity need to be refined further. For a cancer risk assessment at low levels of DNA damage, exposure-related adducts must be discussed in relation to background DNA damage as well as to inter- and intraindividual variability. In rats, subacute ethylene oxide exposures on the order of 1 ppm (1.83 mg/m3) cause DNA adduct levels (HOEtG) of the same magnitude as produced by endogenous ethylene oxide. Based on very recent studies the endogenous background levels of HOEtG in DNA of humans are comparable to those that are produced in rodents by repetitive exogenous ethylene oxide exposures of about 10 ppm (18.3 mg/m3). Experimentally, ethylene oxide has revealed only weak mutagenic effects in vivo, which are confined to higher doses. It has been concluded that long-term human occupational exposure to low airborne

  2. Modeling panic disorder in rodents.

    Science.gov (United States)

    Moreira, Fabrício A; Gobira, Pedro H; Viana, Thércia G; Vicente, Maria A; Zangrossi, Hélio; Graeff, Frederico G

    2013-10-01

    Panic disorder (PD) is a subtype of anxiety disorder in which the core phenomenon is the spontaneous occurrence of panic attacks. Although studies with laboratory animals have been instrumental for the understanding of its neurobiology and treatment, few review articles have focused on the validity of the currently used animal models for studying this psychopathology. Therefore, the aim of the present paper is to discuss the strengths and limits of these models in terms of face, construct and predictive validity. Based on the hypothesis that panic attacks are related to defensive responses elicited by proximal threat, most animal models measure the escape responses induced by specific stimuli. Some apply electrical or chemical stimulation to brain regions proposed to modulate fear and panic responses, such as the dorsal periaqueductal grey or the medial hypothalamus. Other models focus on the behavioural consequences caused by the exposure of rodents to ultrasound or natural predators. Finally, the elevated T-maze associates a one-way escape response from an open arm with panic attacks. Despite some limitations, animal models are essential for a better understanding of the neurobiology and pharmacology of PD and for discovering more effective treatments.

  3. Detection of Toxoplasma gondii by PCR and Mouse Bioassay in Rodents of Ahvaz District, Southwestern Iran

    Directory of Open Access Journals (Sweden)

    J. Saki

    2014-01-01

    Full Text Available Toxoplasma gondii is obligate coccidian zoonotic parasite. Felidae family is definitive and wide ranges of warm-blooded vertebrates are intermediate hosts for the parasite. Rodents are measured as an important source of T. gondii infection for the definitive host. Thus, this study aimed to investigate Toxoplasm infection in rodents of Ahvaz district, southwest of Iran. A total of 100 rodents (73 Rattus norvegicus, 21 Rattus rattus, and 6 Mus musculus were collected and studied by GRA6PCR and mouse bioassay. The finding indicated that 6 out of 100 (6% and 2 out of 100 (2% samples were positive by PCR and mouse bioassay, respectively. The results show notable chronic infection in the rodent and potential transmission of the infection among animal and men in the region. Accordingly, this study recommended investigating of the T. gondii infection in definitive and other intermediate hosts in other points of Khuzestan province, Southwest, Iran.

  4. Anatomical and nutritional adaptations in African rodents

    African Journals Online (AJOL)

    retention time suggest that little ruminant-like fibre digestion occurs in the ... gastro-intestinal tract of rodents (Vorontsov, 1962;. Carleton ... and swollen cells superficially. The fornical .... The ways of food specialization and the evolution of the ...

  5. Detection of genotoxic carcinogens in the in vivo-in vitro hepatocyte DNA repair assay.

    Science.gov (United States)

    Mirsalis, J C; Tyson, C K; Butterworth, B E

    1982-01-01

    The in vivo-in vitro hepatocyte DNA repair assay has been shown to be useful in the evaluation of the carcinogenic potential of chemicals. The purpose of this study was to apply this assay to determining the genotoxicity of the compounds from a wide variety of structural classes. Male Fischer-334 rats were treated by gavage or ip injection with compounds dissolved in either corn oil, water, or dimethyl sulfoxide (DMSO). At selected times after treatment, hepatocytes were isolated by liver perfusion and cultured with 3H-thymidine, Unscheduled DNA synthesis (UDS) was measured by quantitative autoradiography as net grains/nucleus (NG); greater than or equal to 5 NG was considered positive. Water, corn oil, or DMSO controls produced -3 to -6 NG with less than or equal to 6% of the cells in repair. All genotoxic hepatocarcinogens tested produced strong positive responses of greater than 15 NG including dimethylnitrosamine, 2-acetylaminofluorene (2-AAF), azoxymethane, 1,2-dimethylhydrazine, benzidine, aflatoxin B1, 2,6-dinitrotoluene, and 2,4-diaminotoluene. The noncarcinogen, 2,6-diaminotoluene, was negative. The mutagen and rat brain carcinogen methyl methanesulfonate (MMS) and the rat pancreatic carcinogen azaserine were also positive. The carcinogens benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene yielded from -2 to -4 NG. This negative response is consistent with their lack of carcinogenic activity in rat liver. MMS produced the greatest amount of UDS 2 hr after treatment whereas 2-AAF did not induce its maximum response until 12 hr post-treatment. The potent hepatotoxin carbon tetrachloride induced a 40-fold elevation in DNA replication 48 hr after a 400 mg/kg dose, but no UDS was observed at 2, 12, 24, or 48 hr post-treatment. The weak hepatocarcinogen safrole induced no UDS suggesting that it is either nongenotoxic or is metabolized to an active form at an extremely slow rate following a single administration. These results demonstrate that this assay is

  6. Hypericum perforatum as a cognitive enhancer in rodents: A meta-analysis

    Science.gov (United States)

    Ben-Eliezer, Daniel; Yechiam, Eldad

    2016-01-01

    Considered an antidepressant and anti-anxiety agent, Hypericum perforatum affects multiple neurotransmitters in a non-competitive synergistic manner, and may have nootropic potential. We quantitatively reviewed the pre-clinical literature to examine if there is a cognitive-enhancing effect of H. perforatum in healthy rodents. Additionally, within these studies, we compared the effects observed in intact rodents versus those whose performance has been impaired, mostly through stress manipulations. The meta-analysis incorporated studies that examined the effect of H. perforatum versus placebo on memory indices of task performance. All analyses were based on weighting different studies according to their inverse variance. Thirteen independent studies (published 2000–2014) involving 20 experimental comparisons met our inclusion criteria. The results showed a large positive effect of H. perforatum on cognitive performance for intact, healthy rodents (d = 1.11), though a larger effect emerged for stress-impaired rodents (d = 3.10 for restraint stress). The positive effect on intact rodents was observed in tasks assessing reference memory as well as working memory, and was not moderated by the type of memory or motivation (appetitive versus aversive). Thus, while primarily considered as a medication for depression, H. perforatum shows considerable nootropic potential in rodents. PMID:27762349

  7. Hypericum perforatum as a cognitive enhancer in rodents: A meta-analysis.

    Science.gov (United States)

    Ben-Eliezer, Daniel; Yechiam, Eldad

    2016-10-20

    Considered an antidepressant and anti-anxiety agent, Hypericum perforatum affects multiple neurotransmitters in a non-competitive synergistic manner, and may have nootropic potential. We quantitatively reviewed the pre-clinical literature to examine if there is a cognitive-enhancing effect of H. perforatum in healthy rodents. Additionally, within these studies, we compared the effects observed in intact rodents versus those whose performance has been impaired, mostly through stress manipulations. The meta-analysis incorporated studies that examined the effect of H. perforatum versus placebo on memory indices of task performance. All analyses were based on weighting different studies according to their inverse variance. Thirteen independent studies (published 2000-2014) involving 20 experimental comparisons met our inclusion criteria. The results showed a large positive effect of H. perforatum on cognitive performance for intact, healthy rodents (d = 1.11), though a larger effect emerged for stress-impaired rodents (d = 3.10 for restraint stress). The positive effect on intact rodents was observed in tasks assessing reference memory as well as working memory, and was not moderated by the type of memory or motivation (appetitive versus aversive). Thus, while primarily considered as a medication for depression, H. perforatum shows considerable nootropic potential in rodents.

  8. Rodent phylogeny revised: analysis of six nuclear genes from all major rodent clades

    Directory of Open Access Journals (Sweden)

    Pupko Tal

    2009-04-01

    Full Text Available Abstract Background Rodentia is the most diverse order of placental mammals, with extant rodent species representing about half of all placental diversity. In spite of many morphological and molecular studies, the family-level relationships among rodents and the location of the rodent root are still debated. Although various datasets have already been analyzed to solve rodent phylogeny at the family level, these are difficult to combine because they involve different taxa and genes. Results We present here the largest protein-coding dataset used to study rodent relationships. It comprises six nuclear genes, 41 rodent species, and eight outgroups. Our phylogenetic reconstructions strongly support the division of Rodentia into three clades: (1 a "squirrel-related clade", (2 a "mouse-related clade", and (3 Ctenohystrica. Almost all evolutionary relationships within these clades are also highly supported. The primary remaining uncertainty is the position of the root. The application of various models and techniques aimed to remove non-phylogenetic signal was unable to solve the basal rodent trifurcation. Conclusion Sequencing and analyzing a large sequence dataset enabled us to resolve most of the evolutionary relationships among Rodentia. Our findings suggest that the uncertainty regarding the position of the rodent root reflects the rapid rodent radiation that occurred in the Paleocene rather than the presence of conflicting phylogenetic and non-phylogenetic signals in the dataset.

  9. Estimating head and body length in fossil rodents

    NARCIS (Netherlands)

    Freudenthal, M.; Martín-Suárez, E.

    2015-01-01

    We present estimates for head and body length (HBL) of fossil rodents. We assembled HBL data and tooth row length data (LTR, UTR) for a large number of extant rodents, and calculated regression lines of HBL on LTR and UTR for all rodents together (all-rodents equation), and for separate taxonomic gr

  10. Convergent and Divergent Adaptations of Subterranean Rodents

    DEFF Research Database (Denmark)

    Fang, Xiaodong

    Subterranean rodents comprise approximately 250 species that spend their entire lives in underground, unventilated tunnels, distributed along all continents except Australia and Antarctica. Subterranean rodents escape from predators and extreme climatic fluctuations in their underground habitats,......, coupled with the reported genetic information, will promote the utilization of subterranean animal models for biological and biomedical research in the fight against aging, cancer, stroke and other realted diseases....

  11. Investigating the Mechanisms of Action and the Identification of Breast Carcinogens by Computational Analysis of Female Rodent Carcinogena

    Science.gov (United States)

    2004-08-01

    altered sexual differentiation [7,8], immune disturbances [9] as well as no observable adverse effects or even beneficial responses [1]. It has also been...Dacthal Diamyl phthalate - - - Diazinon Dibutyl phthalate - - - Dimethyl isophthalate - - - Dimethyl terephthalate - - - Dinonyl phthalate - - - Dinoseb

  12. Establishing Primary Adult Fibroblast Cultures From Rodents

    Science.gov (United States)

    Seluanov, Andrei; Vaidya, Amita; Gorbunova, Vera

    2010-01-01

    The importance of using primary cells, rather than cancer cell lines, for biological studies is becoming widely recognized. Primary cells are preferred in studies of cell cycle control, apoptosis, and DNA repair, as cancer cells carry mutations in genes involved in these processes. Primary cells cannot be cultured indefinitely due to the onset of replicative senescence or aneuploidization. Hence, new cultures need to be established regularly. The procedure for isolation of rodent embryonic fibroblasts is well established, but isolating adult fibroblast cultures often presents a challenge. Adult rodent fibroblasts isolated from mouse models of human disease may be a preferred control when comparing them to fibroblasts from human patients. Furthermore, adult fibroblasts are the only available material when working with wild rodents where pregnant females cannot be easily obtained. Here we provide a protocol for isolation and culture of adult fibroblasts from rodent skin and lungs. We used this procedure successfully to isolate fibroblasts from over twenty rodent species from laboratory mice and rats to wild rodents such as beaver, porcupine, and squirrel. PMID:20972406

  13. The utility of the small rodent electrocardiogram in toxicology.

    Science.gov (United States)

    Farraj, Aimen K; Hazari, Mehdi S; Cascio, Wayne E

    2011-05-01

    Extensive research has lead to a growing appreciation that the heart is acutely sensitive to a broad array of toxicants via multiple routes of exposure. These agents are as diverse as the antineoplastic drug doxorubicin and environmental agents including ambient air pollution. Adverse effects in the heart often manifest as a change in the electrocardiogram (ECG). The ECG has long been used in the clinic to assess human cardiovascular health. Surface electrocardiographic recordings (i.e., those made from the skin) in humans often help to detect abnormal myocardial impulse formation, conduction, cardiac rhythm disturbances, and altered autonomic regulation of the heart. In toxicology, the ECG provides a collection of end points that may be used to assess both the quality and magnitude of cardiac toxicity. Increasingly over the last two decades, the cardiotoxicity of agents have been characterized using small rodent electrocardiography. Additionally, tremendous insight into possible mechanisms of action of known human cardiotoxicants has been gained. Rat and mouse models offer a number of advantages relative to larger animals including lower cost, less variability, the availability of transgenic models, and a plethora of research tools. Modern day advances in small rodent electrocardiography have enabled assessments in conscious unrestrained animals and improved ECG interpretation. Thus, the incorporation of small rodent electrocardiographic assessments into toxicology studies may facilitate the screening of cardiotoxic potential and the elucidation of mechanisms of action. This review will discuss the utility of the small rodent ECG, various methodologies used to derive ECG data in rats and mice, and various applications in toxicology.

  14. Population response of rodents to control with rodenticides

    Institute of Scientific and Technical Information of China (English)

    S.A.SHILOVA; A.V.TCHABOVSKY

    2009-01-01

    We summarize theoretical approaches and practice of rodent pest control in Russia and former USSR during last 50 years. We review literature as well as original data to understand mechanisms of rodent populations recovery after chemical control campaigns in urban areas, agricultural lands and natural foci of plague. Laboratory and field experiments indicate that inherent individual variation in behavioural, physiological and life-history traits provides survival of heterogeneous mix of individuals in residual population with increased resistance to poisonous baits and high reproductive potential that leads to fast recovery of a population. In a series of field experiments with various rodent and lagomorph species (Mus musculus, Rattus norvegicus, Meriones unguiculatus, M.meridianus, M.tamariscinus, Ochotona pallasii) we have shown that patterns of recolonization of depopulated area and mechanisms of population recovery vary among species and depend on species-specific social organization. After control territorial and group-living species demonstrated an increase in mobility and affiliative and marking behaviour and a decrease in intraspecific aggression. The rate of recolonization of treated areas was high due to redistribution of survived individuals and immigration by neighbors. Population recovered to original level due to increased breeding performance and fecundity of both survived residents and immigrants. In contrast, socially-independent species exhibited minor changes in behaviour. Recolonization was mainly due to better survival and recruitment of youngs, so the rate of recolonization was low. Species-specificity of behavioural compensation mechanisms to control should be considered when developing ecologically based rodent management strategies[Current Zoology 55(2):81-91,2009].

  15. A free energy approach to the prediction of olefin and epoxide mutagenicity and carcinogenicity.

    Science.gov (United States)

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Weeks, Brian; Zimmerman, Julie B; Anastas, Paul T

    2012-12-17

    The mutagenic and carcinogenic effects of strong alkylating agents, such as epoxides, have been attributed to their ability to covalently bind DNA in vivo. Most olefins are readily oxidized to reactive epoxides by CytP450. In an effort to develop predictive models for olefin and epoxide mutagenicity, the ring openings of 15 halogen-, alkyl-, alkenyl-, and aryl-substituted epoxides were modeled by quantum-mechanical transition state calculations using MP2/6-31+G(d,p) in the gas phase and in aqueous solution. Free energies of activation (ΔG(‡)) and free energies of reaction (ΔG(rxn)) were computed for each epoxide in the series. This study finds that an aqueous solution ΔG(rxn) threshold value of approximately -14.7 kcal/mol can be used to discern mutagenic/carcinogenic epoxides (ΔG(rxn) -14.7 kcal/mol). The computed reaction thermodynamics are appropriate regardless of ring-opening mechanism in vivo and are thus proposed as an effective in silico screen and design guideline for decreasing potential mutagenicity and carcinogenicity of olefins and their respective epoxides.

  16. Two-year carcinogenicity study of acrylamide in Wistar Han rats with in utero exposure.

    Science.gov (United States)

    Maronpot, R R; Thoolen, R J M M; Hansen, B

    2015-02-01

    Acrylamide is an important chemical with widespread industrial and other uses in addition to generalized population exposure from certain cooked foods. Previous rat studies to assess the carcinogenic potential of acrylamide have been carried out exclusively in the Fischer 344 rat with identification of a number of tumors amongst which mesotheliomas of the tunica vaginalis is an important tumor endpoint in the classification of acrylamide as a 'probably human carcinogen. In a rat carcinogenicity study to determine the human relevance of mesotheliomas Wistar Han rats were exposed to 0, 0.5, 1.5, or 3.0mg acrylamide/kg body weight/day in drinking water starting at gestation day 6. At the end of two years, mammary gland fibroadenomas in females and thyroid follicular cell tumors in both sexes were the only tumors increased in acrylamide treated rats. These tumor endpoints have rat-specific modes of action suggesting less likelihood of human cancer risk than previously estimated. This study demonstrates that tunica vaginalis mesotheliomas are strain specific and not likely of genotoxic origin.

  17. Orthopox virus infections in Eurasian wild rodents.

    Science.gov (United States)

    Kinnunen, Paula M; Henttonen, Heikki; Hoffmann, Bernd; Kallio, Eva R; Korthase, Christian; Laakkonen, Juha; Niemimaa, Jukka; Palva, Airi; Schlegel, Mathias; Ali, Hanan Sheikh; Suominen, Paula; Ulrich, Rainer G; Vaheri, Antti; Vapalahti, Olli

    2011-08-01

    The genus Orthopoxvirus includes variola (smallpox) virus and zoonotic cowpox virus (CPXV). All orthopoxviruses (OPV) are serologically cross-reactive and cross-protective, and after the cessation of smallpox vaccination, CPXV and other OPV infections represent an emerging threat to human health. In this respect CPXV, with its reservoir in asymptomatically infected wild rodents, is of special importance. In Europe, clinical cowpox has been diagnosed in both humans and animals. The main objective of this study was to elucidate the prevalence of OPV infections in wild rodents in different parts of Eurasia and to compare the performance of three real-time polymerase chain reaction (PCR) methods in detecting OPV DNA in wildlife samples. We investigated 962 wild rodents from Northern Europe (Finland), Central Europe (Germany), and Northern Asia (Siberia, Russia) for the presence of OPV antibodies. According to a CPXV antigen-based immunofluorescence assay, animals from 13 of the 17 locations (76%) showed antibodies. Mean seroprevalence was 33% in Finland (variation between locations 0%-69%), 32% in Germany (0%-43%), and 3.2% (0%-15%) in Siberia. We further screened tissue samples from 513 of the rodents for OPV DNA using up to three real-time PCRs. Three rodents from two German and one Finnish location were OPV DNA positive. The amplicons were 96% to 100% identical to available CPXV sequences. Further, we demonstrated OPV infections as far east as the Baikal region and occurring in hamster and two other rodent species, ones previously unnoticed as possible reservoir hosts. Based on serological and PCR findings, Eurasian wild rodents are frequently but nonpersistently infected with OPVs. Results from three real-time PCR methods were highly concordant. This study extends the geographic range and wildlife species diversity in which OPV (or CPXV) viruses are naturally circulating.

  18. Leishmania infantum in wild rodents: reservoirs or just irrelevant incidental hosts?

    Science.gov (United States)

    Navea-Pérez, H M; Díaz-Sáez, V; Corpas-López, V; Merino-Espinosa, G; Morillas-Márquez, F; Martín-Sánchez, J

    2015-06-01

    Wild rodents constitute a very large biomass of potential reservoirs for Leishmania spp. Therefore, an epidemiological study was carried out in a well-known focus of canine leishmaniasis from southern Spain, with the objective of detecting and characterizing Leishmania infantum infection in wild rodents. Blood, liver, spleen, bone marrow, and skin from 37 rodents (24 Apodemus sylvaticus, 9 Rattus rattus, and 4 Mus musculus) were analyzed by optical microscopy, culture, and two different polymerase chain reactions. L. infantum DNA was found in 27% (10 out of 37) of the trapped rodents, in a variety of tissues: bone marrow, spleen, or healthy skin (ear lobe). High prevalences of L. infantum infection were found in the three investigated rodent species. The presence of other trypanosomatids was also evidenced. These rodent species are abundant, widely distributed in Europe, and have a long enough lifespan to overcome the low sandfly activity season. They live in a suitable habitat for sandflies and serve as blood sources for these insects, which can become infected when induced to feed on Leishmania-infected animals. Whether they are reservoirs or just irrelevant incidental hosts, it is clear that the epidemiology of L. infantum is more complex than previously thought, and so is its control. The classic epidemiological cycle dog-sandfly-human is turning into a network of animal species that collaborate with the dog in the maintenance of the parasite under natural conditions and probably showing local differences.

  19. The past, present, and future of National Aeronautics and Space Administration spaceflight diet in support of microgravity rodent experiments.

    Science.gov (United States)

    Sun, Gwo-Shing; Tou, Janet C; Yu, Diane; Girten, Beverly E; Cohen, Jacob

    2014-02-01

    Rodents have been the most frequently flown animal model used to study physiological responses to the space environment. In support of future of space exploration, the National Aeronautics and Space Administration (NASA) envisions an animal research program focused on rodents. Therefore, the development of a rodent diet that is suitable for the spaceflight environment including long duration spaceflight is a high priority. Recognizing the importance of nutrition in affecting spaceflight physiological responses and ensuring reliable biomedical and biological science return, NASA developed the nutrient-upgraded rodent food bar (NuRFB) as a standard diet for rodent spaceflight. Depending on future animal habitat hardware and planned spaceflight experiments, modification of the NuRFB or development of a new diet formulation may be needed, particularly for long term spaceflights. Research in this area consists primarily of internal technical reports that are not readily accessible. Therefore, the aims of this contribution are to provide a brief history of the development of rodent spaceflight diets, to review the present diet used in rodent spaceflight studies, and to discuss some of the challenges and potential solutions for diets to be used in future long-term rodent spaceflight studies.

  20. Small rodents as paratenic or intermediate hosts of carnivore parasites in Berlin, Germany

    Science.gov (United States)

    Maaz, Denny; Demeler, Janina; Ramünke, Sabrina; Antolová, Daniela; Schaper, Roland; von Samson-Himmelstjerna, Georg

    2017-01-01

    Rodents are important intermediate and paratenic hosts for carnivore parasites, including the important zoonotic agents Toxoplasma, Echinococcus and Toxocara. Monitoring of such parasites in rodents can be used to detect increasing risks for human and veterinary public health. Rodents were trapped at four sites in Berlin, two near the city center, two at the periphery. PCRs were conducted to detect Coccidia (target ITS-1) and specifically Toxoplasma gondii (repetitive element) in brain and ascarids (ITS-2) in muscle or brain tissue. During necropsies, metacestodes were collected and identified using ITS-2 and 12S rRNA PCRs. An ELISA to detect antibodies against Toxocara canis ES antigens was performed. Within the 257 examined rodents, the most frequently observed parasite was Frenkelia glareoli predominantly found in Myodes glareolus. T. gondii was only detected in 12 rodents and Microtus spp. (although strongly underrepresented) had a significantly increased chance of being positive. Neither Echinococcus nor typical Taenia parasites of dogs and cats were found but Mesocestoides litteratus and Taenia martis metacestodes were identified which can cause severe peritoneal or ocular cysticercosis in dogs, primates and humans. Using PCR, the ascarids T. canis (n = 8), Toxocara cati (4) and Parascaris sp. (1) were detected predominantly in muscles. Seroprevalence of T. canis was 14.2% and ELISA was thus more sensitive than PCR to detect infection with this parasite. Non-parametric multidimensional scaling and cluster analysis revealed that parasite communities could be grouped into an urban and a peri-urban cluster with high frequency of ascarid-positive rodents in urban and high frequency of F. glareoli in peri-urban sites. Prevalence rates of parasites in rodents with potential impact for human or veterinary public health are considerable and the monitoring of transmission cycles of carnivore parasites in intermediate rodent hosts is recommended to estimate the health

  1. Chemical characteristic of PM2.5 emission and inhalational carcinogenic risk of domestic Chinese cooking.

    Science.gov (United States)

    Zhang, Nan; Han, Bin; He, Fei; Xu, Jia; Zhao, Ruojie; Zhang, Yujuan; Bai, Zhipeng

    2017-08-01

    To illustrate chemical characteristic of PM2.5 emission and assess inhalational carcinogenic risk of domestic Chinese cooking, 5 sets of duplicate cooking samples were collected, using the most used 5 types of oil. The mass abundance of 14 elements, 5 water-soluble ions, organic carbon (OC), elemental carbon (EC) and 11 polycyclic aromatic hydrocarbons (PAHs) were calculated; the signature and diagnostic ratio of cooking in the domestic kitchen were analyzed; and carcinogenic risks of heavy metals and PAHs via inhalation were assessed in two scenarios. The analysis showed that OC was the primary composition in the chemical profile; Na was the most abundant element that might be due to the usage of salt; Cr and Pb, NO3(-) and SO4(2-), Phe, FL and Pyr were the main heavy metals/water-soluble ions/PAHs, respectively. Phe and FL could be used to separate cooking and stationary sources, while diagnostic ratios of BaA/(BaA + CHR), BaA/CHR, BaP/BghiP and BaP/BeP should be applied with caution, as they were influenced by various cooking conditions. Carcinogenic risks of heavy metals and PAHs were evaluated in two scenarios, simulating the condition of cooking with no ventilation and with the range hood on, respectively. The integrated risk of heavy metals and PAHs was 2.7 × 10(-3) and 5.8 × 10(-6), respectively, during cooking with no ventilation. While with the usage of range hood, only Cr(VI), As and Ni might induce potential carcinogenic risk. The difference in the chemical abundance in cooking sources found between this and other studies underlined the necessity of constructing locally representative source profiles under real conditions. The comparison of carcinogenic risk suggested that the potentially adverse health effects induced by inorganic compositions from cooking sources should not be ignored. Meanwhile, intervention methods, such as the operation of range hood, should be applied during cooking for health protection. Copyright © 2017 Elsevier Ltd

  2. Cannabis and tobacco smoke are not equally carcinogenic

    Directory of Open Access Journals (Sweden)

    Melamede Robert

    2005-10-01

    Full Text Available Abstract More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke contains nicotine. Available scientific data, that examines the carcinogenic properties of inhaling smoke and its biological consequences, suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer.

  3. Carcinogenicity in rats of the SGLT2 inhibitor canagliflozin.

    Science.gov (United States)

    De Jonghe, Sandra; Proctor, Jim; Vinken, Petra; Feyen, Bianca; Wynant, Inneke; Marien, Dirk; Geys, Helena; Mamidi, Rao N V S; Johnson, Mark D

    2014-12-05

    The carcinogenicity potential of canagliflozin, an inhibitor of SGLT2, was evaluated in a 2-year rat study (10, 30, and 100 mg/kg). Rats showed an increase in pheochromocytomas, renal tubular tumors, and testicular Leydig cell tumors. Systemic exposure multiples at the highest dose relative to the maximum clinical dose were 12- to 21-fold. Pheochromocytomas and renal tubular tumors were noted in both sexes at 100 mg/kg. Leydig cell tumors were observed in males in all dose groups and were associated with increased luteinizing hormone levels. Hyperplasia was increased in the adrenal medulla at 100 mg/kg, but only a limited increase in simple tubular hyperplasia was observed in the kidney of males at 100 mg/kg. Hyperostosis occurred and was accompanied by substantial effects on calcium metabolism, including increased urinary calcium excretion and decreased levels of calcium regulating hormones (1,25-dihydroxyvitamin D and parathyroid hormone). A separate study with radiolabeled calcium confirmed that increased urinary calcium excretion was mediated via increased calcium absorption from the gastrointestinal tract. It was hypothesized that, at high doses, canagliflozin might have inhibited glucose absorption in the intestine via SGLT1 inhibition that resulted in glucose malabsorption, which increased calcium absorption by stimulating colonic glucose fermentation and reducing intestinal pH. Pheochromocytomas and adrenal medullary hyperplasia were attributed to altered calcium homeostasis, which have a known relationship in the rat. In conclusion, Leydig cell tumors were associated with increased luteinizing hormone levels and pheochromocytomas were most likely related to glucose malabsorption and altered calcium homeostasis. Renal tubular tumors may also have been linked to glucose malabsorption. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Endoparasites of Wild Rodents in Southeastern Iran

    Directory of Open Access Journals (Sweden)

    Mehdi Nateghpour

    2015-10-01

    Full Text Available Background: This study was aimed to collect wild rodents for endoparasites determination in some parts of Sistan and Baluchistan Province, southeastern Iran nearby Pakistan and Afghanistan countries.Methods: A total of 100 wild rodents were captured alive with cage traps. Various samples were collected from blood and feces, also impression smear prepared from different organs. The samples were prepared by formalin-ether or stained with Giemsa, after that were examined under microscope.Results: All the caught rodents (47 Tatera indica, 44 Meriones hurriana, 5 Gerbilus nanus and 4 Meriones libycus were studied for endoparasites emphasizing to their zoonotic aspects. Endoparasites including Spirurida,Hymenolepis diminuta, Hymenolepis nana feraterna, Trichuris trichiura, Skerjabino taenia, Trichostrongylus spp, Entamoeba muris, Chilomastix mesnili and Leishmania spp were parasitologically identified.Conclusion: Among 9 genera or species of the identified parasites at least 5 of them have zoonotic and public health importance.

  5. The MAM rodent model of schizophrenia.

    Science.gov (United States)

    Lodge, Daniel J

    2013-01-01

    Rodent models of human disease are essential to obtain a better understanding of disease pathology, the mechanism of action underlying conventional treatments, as well as for the generation of novel therapeutic approaches. There are a number of rodent models of schizophrenia based on either genetic manipulations, acute or sub-chronic drug administration, or developmental disturbances. The prenatal methylazoxymethanol acetate (MAM) rodent model is a developmental disruption model gaining increased attention because it displays a number of histological, neurophysiological, and behavioral deficits analogous to those observed in schizophrenia patients. This unit describes the procedures required to safely induce the MAM phenotype in rats. In addition, we describe a simple behavioral procedure, amphetamine-induced hyperlocomotion, which can be utilized to verify the MAM phenotype.

  6. Developmental toxicity of engineered nanomaterials in rodents.

    Science.gov (United States)

    Ema, Makoto; Gamo, Masashi; Honda, Kazumasa

    2016-05-15

    We summarized significant effects reported in the literature on the developmental toxicity of engineered nanomaterials (ENMs) in rodents. The developmental toxicity of ENMs included not only structural abnormalities, but also death, growth retardation, and behavioral and functional abnormalities. Most studies were performed on mice using an injection route of exposure. Teratogenic effects were indicated when multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), and TiO2-nanoparticles were administered to mice during early gestation. Reactive oxygen species levels were increased in placentas and malformed fetuses and their placentas after prenatal exposure to MWCNTs and SWCNTs, respectively. The pre- and postnatal mortalities and growth retardation in offspring increased after prenatal exposure to ENMs. Histopathological and functional abnormalities were also induced in placentas after prenatal exposure to ENMs. Maternal exposure to ENMs induced behavioral alterations, histopathological and biochemical changes in the central nervous system, increased susceptibility to allergy, transplacental genotoxicity, and vascular, immunological, and reproductive effects in offspring. The size- and developmental stage-dependent placental transfer of ENMs was noted after maternal exposure. Silver accumulated in the visceral yolk sac after being injected with Ag-NPs during early gestation. Although currently available data has provided initial information on the potential developmental toxicity of ENMs, that on the developmental toxicity of ENMs is still very limited. Further studies using well-characterized ENMs, state-of the-art study protocols, and appropriate routes of exposure are required in order to clarify these developmental effects and provide information suitable for risk assessments of ENMs.

  7. Micronucleus test in rodent tissues other than liver or erythrocytes: Report of the IWGT working group.

    Science.gov (United States)

    Uno, Yoshifumi; Morita, Takeshi; Luijten, Mirjam; Beevers, Carol; Hamada, Shuichi; Itoh, Satoru; Ohyama, Wakako; Takasawa, Hironao

    2015-05-01

    At the 6th International Workshop on Genotoxicity Testing, the liver micronucleus test (MNT) working group briefly discussed the MNT using tissues other than liver/erythrocytes. Many tissues other than liver/erythrocytes have been studied, primarily for research purposes. They have included the colon and intestinal epithelium, skin, spleen, lung, stomach, bladder, buccal mucosa, vagina, and fetal/neonatal tissues. These tissues were chosen because they were target sites of carcinogens, and/or relevant to a specific route of exposure. Recently, there has been particular focus on the gastrointestinal (GI) tract as it is a contact site associated with high exposure following oral gavage. Furthermore GI tumors are observed with high frequency in human populations. A collaborative study of the rat glandular stomach and colon MNT was conducted in conjunction with a collaborative study of the repeated-dose liver MNT. Based on limited data currently available, the rodent MNT using the glandular stomach and/or colon seems to detect genotoxic carcinogens with GI tract target-organ specificity. The working group concluded that the GI tract MNT would be a promising method to examine clastogenicity or aneugenicity of test chemicals in the stomach and/or colon. Further data will be needed to fully establish the methods, and to identify the sensitivity and specificity of the GI tract MNT.

  8. Use of in silico models for prioritization of heat-induced food contaminants in mutagenicity and carcinogenicity testing.

    Science.gov (United States)

    Frenzel, Falko; Buhrke, Thorsten; Wenzel, Irina; Andrack, Jennifer; Hielscher, Jan; Lampen, Alfonso

    2017-01-16

    Numerous Maillard reaction and lipid oxidation products are present in processed foods such as heated cereals, roasted meat, refined oils, coffee, and juices. Due to the lack of experimental toxicological data, risk assessment is hardly possible for most of these compounds. In the present study, an in silico approach was employed for the prediction of the toxicological endpoints mutagenicity and carcinogenicity on the basis of the structure of the respective compound, to examine (quantitative) structure-activity relationships for more than 800 compounds. Five software tools for mutagenicity prediction (T.E.S.T., SARpy, CAESAR, Benigni-Bossa, and LAZAR) and three carcinogenicity prediction tools (CAESAR, Benigni-Bossa, and LAZAR) were combined to yield so-called mutagenic or carcinogenic scores for every single substance. Alcohols, ketones, acids, lactones, and esters were predicted to be mutagenic and carcinogenic with low probability, whereas the software tools tended to predict a considerable mutagenic and carcinogenic potential for thiazoles. To verify the in silico predictions for the endpoint mutagenicity experimentally, twelve selected compounds were examined for their mutagenic potential using two different validated in vitro test systems, the bacterial reverse mutation assay (Ames test) and the in vitro micronucleus assay. There was a good correlation between the results of the Ames test and the in silico predictions. However, in the case of the micronucleus assay, at least three substances, 2-amino-6-methylpyridine, 6-heptenoic acid, and 2-methylphenol, were clearly positive although they were predicted to be non-mutagenic. Thus, software tools for mutagenicity prediction are suitable for prioritization among large numbers of substances, but these predictions still need experimental verification.

  9. Development of a Medium-term Animal Model Using gpt Delta Rats to Evaluate Chemical Carcinogenicity and Genotoxicity

    Science.gov (United States)

    Matsushita, Kohei; Kijima, Aki; Ishii, Yuji; Takasu, Shinji; Jin, Meilan; Kuroda, Ken; Kawaguchi, Hiroaki; Miyoshi, Noriaki; Nohmi, Takehiko; Ogawa, Kumiko; Umemura, Takashi

    2013-01-01

    In this study, the potential for development of an animal model (GPG46) capable of rapidly detecting chemical carcinogenicity and the underlying mechanisms of action were examined in gpt delta rats using a reporter gene assay to detect mutations and a medium-term rat liver bioassay to detect tumor promotion. The tentative protocol for the GPG46 model was developed based on the results of dose-response exposure to diethylnitrosamine (DEN) and treatment with phenobarbital over time following DEN administration. Briefly, gpt delta rats were exposed to various chemicals for 4 weeks, followed by a partial hepatectomy (PH) to collect samples for an in vivo mutation assay. The mutant frequencies (MFs) of the reporter genes were examined as an indication of tumor initiation. A single intraperitoneal (ip) injection of 10 mg/kg DEN was administered to rats 18 h after the PH to initiate hepatocytes. Tumor-promoting activity was evaluated based on the development of glutathione S-transferase placental form (GST-P)-positive foci at week 10. The genotoxic carcinogens 2-acetylaminofluorene (2-AAF), 2-amino-3-methylimidazo [4,5-f] quinolone (IQ) and safrole (SF), the non-genotoxic carcinogens piperonyl butoxide (PBO) and phenytoin (PHE), the non-carcinogen acetaminophen (APAP) and the genotoxic non-hepatocarcinogen aristolochic acid (AA) were tested to validate the GPG46 model. The validation results indicate that the GPG46 model could be a powerful tool in understanding chemical carcinogenesis and provide valuable information regarding human risk hazards. PMID:23723564

  10. Effects of combined exposure of F344 rats to inhaled Plutonium-239 dioxide and a chemical carcinogen (NNK)

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D.L.; Carlton, W.W. [Purdue Univ., Lafayette, IN (United States); Griffith, W.C. [and others

    1995-12-01

    Workers in nuclear weapons facilities have a significant potential for exposure to chemical carcinogens and to radiation from external sources or from internally deposited radionuclides such as {sup 239}Pu. Although the carcinogenic effects of inhaled {sup 239}Pu and many chemicals have been studied individually, very little information is available on their combined effects. One chemical carcinogen that workers could be exposed to via tobacco smoke is the tobacco-specific nitrosamine 4-(N-methyl-n-nitrosamino)-1-(3-pyridyl)-1(3-pyridyl)-1-butanone (NNK), a product of tobacco curing and the pyrolysis of nicotine in tobacco. NNK causes lung tumors in rats, regardless of the route of administration and to a lesser extent liver, nasal, and pancreatic tumors. From the results presented, it can be concluded that exposure to a chemical carcinogen (NNK) in combination with {alpha}-particle radiation from inhaled {sup 239}PuO{sub 2} acts in, at best, an additive manner in inducing lung cancer in rats.

  11. Rodent models of ischemic stroke lack translational relevance... are baboon models the answer?

    Science.gov (United States)

    Kwiecien, Timothy D; Sy, Christopher; Ding, Yuchuan

    2014-05-01

    Rodent models of ischemic stroke are associated with many issues and limitations, which greatly diminish the translational potential of these studies. Recent studies demonstrate that significant differences exist between rodent and human ischemic stroke. These differences include the physical characteristics of the stroke, as well as changes in the subsequent inflammatory and molecular pathways following the acute ischemic insult. Non-human primate (NHP) models of ischemic stroke, however, are much more similar to humans. In addition to evident anatomical similarities, the physiological responses that NHPs experience during ischemic stroke are much more applicable to the human condition and thus make it an attractive model for future research. The baboon ischemic stroke model, in particular, has been studied extensively in comparison to other NHP models. Here we discuss the major shortcomings associated with rodent ischemic stroke models and provide a comparative overview of baboon ischemic stroke models. Studies have shown that baboons, although more difficult to obtain and handle, are more representative of ischemic events in humans and may have greater translational potential that can offset these deficiencies. There remain critical issues within these baboon stroke studies that need to be addressed in future investigations. The most critical issue revolves around the size and the variability of baboon ischemic stroke. Compared to rodent models, however, issues such as these can be addressed in future studies. Importantly, baboon models avoid many drawbacks associated with rodent models including vascular variability and inconsistent inflammatory responses - issues that are inherent to the species and cannot be avoided.

  12. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

    NARCIS (Netherlands)

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic

  13. Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk

    NARCIS (Netherlands)

    Rietjens, I.M.C.M.; Boersma, M.G.; Woude, van der H.; Jeurissen, S.M.F.; Schutte, M.E.; Alink, G.M.

    2005-01-01

    The present review focuses on the mechanisms of mutagenic action and the carcinogenic risk of two categories of botanical ingredients, namely the flavonoids with quercetin as an important bioactive representative, and the alkenylbenzenes, namely safrole, methyleugenol and estragole. For quercetin a

  14. An Interdisciplinary and Alternative Approach to Assess Carcinogenicity of Chlorobenzenes.

    Science.gov (United States)

    2007-11-02

    carcinogenic activity of 1,4-di-, 1,2,4,5-tetra-, penta-, and hexa - chlorobenzenes in the Ito’s "Medium-Term Bioassay System" using partially...GST-P positive foci and related morphometric analyses, gene expressions of CYP1 A2, c-fos, c-jun, GSH/GSSG ratio, tissue porphyrin levels, DNA damage

  15. Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Beyersmann, Detmar [University of Bremen (Germany). Biochemistry, Department of Biology and Chemistry; Hartwig, Andrea [Technical University of Berlin (Germany). Institute of Food Technology and Food Chemistry

    2008-08-15

    Mechanisms of carcinogenicity are discussed for metals and their compounds, classified as carcinogenic to humans or considered to be carcinogenic to humans: arsenic, antimony, beryllium, cadmium, chromium, cobalt, lead, nickel and vanadium. Physicochemical properties govern uptake, intracellular distribution and binding of metal compounds. Interactions with proteins (e.g., with zinc finger structures) appear to be more relevant for metal carcinogenicity than binding to DNA. In general, metal genotoxicity is caused by indirect mechanisms. In spite of diverse physicochemical properties of metal compounds, three predominant mechanisms emerge: (1) interference with cellular redox regulation and induction of oxidative stress, which may cause oxidative DNA damage or trigger signaling cascades leading to stimulation of cell growth; (2) inhibition of major DNA repair systems resulting in genomic instability and accumulation of critical mutations; (3) deregulation of cell proliferation by induction of signaling pathways or inactivation of growth controls such as tumor suppressor genes. In addition, specific metal compounds exhibit unique mechanisms such as interruption of cell-cell adhesion by cadmium, direct DNA binding of trivalent chromium, and interaction of vanadate with phosphate binding sites of protein phosphatases. (orig.)

  16. Binding of chemical carcinogens to macromolecules in cultured human colon

    DEFF Research Database (Denmark)

    1977-01-01

    Metabolic activation of different chemical classes of carcinogens was studied in cultured human colon epithelia. Human colon epithelia were maintained in explant culture up to 4 days. Binding of benzo(a)pyrene, dimethylnitrosamine, and 1,2- dimethylhydrazine was found in both cell DNA and protein....... 1,2-Dimethylhydrazine methylated DNA at both N·7 and 0-6 positions of guanin....

  17. 18. Adduct detection in human monitoring for carcinogen exposure

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Determination of the covalently bound products (adducts) of carcinogens with DNA or proteins may be used for the monitoring of exposure to these compounds. Protein adducts are generally stable and are not enzymatically repaired, and the use of these for cxposure monitoring is normally carried out with globin or albumin, because

  18. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

    NARCIS (Netherlands)

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans|info:eu-repo/dai/nl/074385224; Hansen, Johnni; Guyton, Kathryn Z.

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studie

  19. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    NARCIS (Netherlands)

    Pearce, Neil E; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier A; Birnbaum, Linda S; Brownson, Ross C; Bucher, John R; Cantor, Kenneth P; Cardis, Elisabeth; Cherrie, John W; Christiani, David C; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A; Dement, John M; Douwes, Jeroen; Eisen, Ellen A; Engel, Lawrence S; Fenske, Richard A; Fleming, Lora E; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H; Lynch, Charles F; Lynge, Elsebeth; 't Mannetje, Andrea; McMichael, Anthony J; McLaughlin, John R; Marrett, Loraine; Martuzzi, Marco; Merchant, James A; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E; Monson, Richard; Nordby, Karl-Kristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela C; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M; Rushton, Lesley; Rusiecki, Jennifer A; Rusyn, Ivan; Samet, Jonathan M; Sandler, Dale P; de Sanjose, Silvia; Schernhammer, Eva; Seniori Constantini, Adele; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silvermann, Debra T; Simonato, Lorenzo; Smith, Allan H; Smith, Martyn T; Spinelli, John J; Spitz, Margaret R; Stallones, Lorann; Stayner, Leslie T; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W; Stewart, Patricia A; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G; Ward, Elizabeth M; Weinberg, Clarice R; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia H

    2015-01-01

    BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' fa

  20. Non—Genotoxic Carcinogens.Approaches to Their Rish Assessment

    Institute of Scientific and Technical Information of China (English)

    J.A.CASTRO; M.I.DiazGomez; 等

    1993-01-01

    Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment.In turn,chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechanisms.There were described in literature several simple rapid and inexpensive short term ests to reasonably predict the genotoxic nature of chemicals but in contrast,there is no reliable test or battery of tests available to predict the carcinogenicity of non-genotoxic compounds and this poses a major problem to their rish assessment.In addition,there are conflictive opinions about rish assessment needs for both classes of carcinogens.Some workers elieve that for non-genotoxic carcinogens,thresholds for exposure can be drawn while others do not.In this review,the reasons behind both of these opinions and the present hypotheses about the mechanism of action of non-genotoxic carcinogens are described and analyzed in relation to future needs.

  1. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    NARCIS (Netherlands)

    Pearce, Neil E; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier A; Birnbaum, Linda S; Brownson, Ross C; Bucher, John R; Cantor, Kenneth P; Cardis, Elisabeth; Cherrie, John W; Christiani, David C; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A; Dement, John M; Douwes, Jeroen; Eisen, Ellen A; Engel, Lawrence S; Fenske, Richard A; Fleming, Lora E; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H; Lynch, Charles F; Lynge, Elsebeth; 't Mannetje, Andrea; McMichael, Anthony J; McLaughlin, John R; Marrett, Loraine; Martuzzi, Marco; Merchant, James A; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E; Monson, Richard; Nordby, Karl-Kristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela C; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M; Rushton, Lesley; Rusiecki, Jennifer A; Rusyn, Ivan; Samet, Jonathan M; Sandler, Dale P; de Sanjose, Silvia; Schernhammer, Eva; Seniori Constantini, Adele; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silvermann, Debra T; Simonato, Lorenzo; Smith, Allan H; Smith, Martyn T; Spinelli, John J; Spitz, Margaret R; Stallones, Lorann; Stayner, Leslie T; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W; Stewart, Patricia A; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G; Ward, Elizabeth M; Weinberg, Clarice R; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia H

    2015-01-01

    BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' fa

  2. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    NARCIS (Netherlands)

    Pearce, Neil E; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier A; Birnbaum, Linda S; Brownson, Ross C; Bucher, John R; Cantor, Kenneth P; Cardis, Elisabeth; Cherrie, John W; Christiani, David C; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A; Dement, John M; Douwes, Jeroen; Eisen, Ellen A; Engel, Lawrence S; Fenske, Richard A; Fleming, Lora E; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick|info:eu-repo/dai/nl/072910542; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans|info:eu-repo/dai/nl/074385224; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H; Lynch, Charles F; Lynge, Elsebeth; 't Mannetje, Andrea; McMichael, Anthony J; McLaughlin, John R; Marrett, Loraine; Martuzzi, Marco; Merchant, James A; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E; Monson, Richard; Nordby, Karl-Kristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela C; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M; Rushton, Lesley; Rusiecki, Jennifer A; Rusyn, Ivan; Samet, Jonathan M; Sandler, Dale P; de Sanjose, Silvia; Schernhammer, Eva; Seniori Constantini, Adele; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silvermann, Debra T; Simonato, Lorenzo; Smith, Allan H; Smith, Martyn T; Spinelli, John J; Spitz, Margaret R; Stallones, Lorann; Stayner, Leslie T; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W; Stewart, Patricia A; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E; Vainio, Harri; Vena, John; Vermeulen, Roel|info:eu-repo/dai/nl/216532620; Victora, Cesar G; Ward, Elizabeth M; Weinberg, Clarice R; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia H

    2015-01-01

    BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups'

  3. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

    NARCIS (Netherlands)

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studie

  4. Cell-mediated mutagenesis and cell transformation by chemical carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Huberman, E.; Langenbach, R.

    1977-01-01

    Results are reported from studies that showed that mutagenesis of mammalian cells can be achieved by carcinogenic polycyclic hydrocarbons, nitrosamines, and aflatoxins when tested in the presence of fibroblasts and hepatocytes which are able to metabolize these carcinogens. Further, we have found that there is a relationship between the degree of mutant induction and the degree of carcinogenicity of the different chemicals tested. By simultaneously measuring the frequency of cell transformation and the frequency of mutation at one locus (ouabain resistance) in the same cell system, it was possible to estimate the genetic target site for cell transformation. The results indicated that the target site for transformation is approximately 20 times larger than that determined for ouabain resistance. The results suggest that cell transformation may be due to a mutational event and the mutation can occur in one out of a small number of the same or different genes, and that the cell-mediated mutagenesis approach may be a valuable means of detecting tissue-specific carcinogens.

  5. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    Science.gov (United States)

    Carcinogenic Effects of Low Doses of Ionizing RadiationR Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711The form of the dose-response curve for radiation-induced cancers, particu...

  6. Protozoan Parasites of Rodents and Their Zoonotic Significance in Boyer-Ahmad District, Southwestern Iran

    Directory of Open Access Journals (Sweden)

    Zeinab Seifollahi

    2016-01-01

    Full Text Available Backgrounds. Wild rodents are reservoirs of various zoonotic diseases, such as toxoplasmosis, babesiosis, and leishmaniasis. The current study aimed to assess the protozoan infection of rodents in Boyer-Ahmad district, southwestern Iran. Materials and Methods. A total of 52 rodents were collected from different parts of Boyer-Ahmad district, in Kohgiluyeh and Boyer-Ahmad province, using Sherman live traps. Each rodent was anesthetized with ether, according to the ethics of working with animals, and was dissected. Samples were taken from various tissues and stool samples were collected from the contents of the colon and small intestines. Moreover, 2 to 5 mL of blood was taken from each of the rodents and the sera were examined for anti-Leishmania antibodies, by ELISA, or anti-T. gondii antibodies, by modified agglutination test (MAT. DNA was extracted from brain tissue samples of each rodent and PCR was used to identify the DNA of T. gondii. Results. Of the 52 stool samples of rodents studied by parasitological methods, intestinal protozoa infection was seen in 28 cases (53.8%. From 52 rodents, 19 (36.5% were infected with Trichomonas, 10 (19.2% with Giardia muris, and 11 (21.2% with Entamoeba spp. Also, 10 cases (19.2% were infected with Blastocystis, 3 (5.8% were infected with Chilomastix, 7 (13.5% were infected with Endolimax, 1 (1.9% was infected with Retortamonas, 3 (5.77% were infected with T. gondii, and 6 (11.54% were infected with Trypanosoma lewisi. Antibodies to T. gondii were detected in the sera of 5 (9.61% cases. Results of the molecular study showed T. gondii infection in 3 (5.77% of the rodents. Findings of this study showed that rodents in Kohgiluyeh and Boyer-Ahmad province, southwestern Iran, are infected with several blood and intestinal parasites; some of them might be potential risks to residents and domestic animals in the region.

  7. Object Recognition Memory and the Rodent Hippocampus

    Science.gov (United States)

    Broadbent, Nicola J.; Gaskin, Stephane; Squire, Larry R.; Clark, Robert E.

    2010-01-01

    In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR…

  8. Rodent malaria parasites : genome organization & comparative genomics

    NARCIS (Netherlands)

    Kooij, Taco W.A.

    2006-01-01

    The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P. falciparu

  9. Rodent malaria parasites : genome organization & comparative genomics

    NARCIS (Netherlands)

    Kooij, Taco W.A.

    2006-01-01

    The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P.

  10. Neurogenic inflammation in human and rodent skin

    DEFF Research Database (Denmark)

    Schmelz, M; Petersen, Lars Jelstrup

    2001-01-01

    The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...... about neurogenic inflammation in human skin, including the involvement of mast cells....

  11. Estimating body mass of fossil rodents

    NARCIS (Netherlands)

    Freudenthal, M.; Martín-Suárez, E.

    2013-01-01

    Reconstructing the body mass of a fossil animal is an essential step toward understanding its palaeoecological role. Length × width (L×W) of the first lower molar (m1) is frequently used as a proxy for body mass in fossil mammals. However, among rodents, Muroidea have no premolar and an elongated m1

  12. Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

    OpenAIRE

    Hecht, S

    2004-01-01

    Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts.

  13. Genotoxic and carcinogenic risks associated with the dietary consumption of repeatedly heated coconut oil.

    Science.gov (United States)

    Srivastava, Smita; Singh, Madhulika; George, Jasmine; Bhui, Kulpreet; Murari Saxena, Anand; Shukla, Yogeshwer

    2010-11-01

    Repeated heating of vegetable oils at high temperatures during cooking is a very common cooking practice. Repeated heating of edible oils can generate a number of compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have been reported to have carcinogenic potential. Consumption of these repeatedly heated oils can pose a serious health hazard. The objectives of the present study were to evaluate the genotoxic and carcinogenic risks associated with the consumption of repeatedly heated coconut oil (RCO), which is one of the commonly consumed cooking and frying medium. The PAH were analysed using HPLC in fresh CO, single-heated CO (SCO) and RCO. Results revealed the presence of certain PAH, known to possess carcinogenic potential, in RCO when compared with SCO. Oral intake of RCO in Wistar rats resulted in a significant induction of aberrant cells (P<0·05) and micronuclei (P<0·05) in a dose-dependent manner. Oxidative stress analysis showed a significant (P<0·05) decrease in the levels of antioxidant enzymes such as superoxide dismutase and catalase with a concurrent increase in reactive oxygen species and lipid peroxidation in the liver. In addition, RCO given alone and along with diethylnitrosamine for 12 weeks induced altered hepatic foci as noticed by alteration in positive (γ-glutamyl transpeptidase and glutathione-S-transferase) and negative (adenosine triphosphatase, alkaline phosphatase and glucose-6-phosphatase) hepatospecific biomarkers. A significant decrease in the relative and absolute hepatic weight of RCO-supplemented rats was recorded (P<0·05). In conclusion, dietary consumption of RCO can cause a genotoxic and preneoplastic change in the liver.

  14. Biodegradation of the metallic carcinogen hexavalent chromium Cr(VI by an indigenously isolated bacterial strain

    Directory of Open Access Journals (Sweden)

    Das Alok

    2010-01-01

    Full Text Available Background : Hexavalent chromium [Cr(VI], a potential mutagen and carcinogen, is regularly introduced into the environment through diverse anthropogenic activities, including electroplating, leather tanning, and pigment manufacturing. Human exposure to this toxic metal ion not only causes potential human health hazards but also affects other life forms. The World Health Organization, the International Agency for Research on Cancer, and the Environmental Protection Agency have determined that Cr(VI compounds are known human carcinogens. The Sukinda valley in Jajpur District, Orissa, is known for its deposit of chromite ore, producing nearly 98% of the chromite ore in India and one of the prime open cast chromite ore mines in the world (CES, Orissa Newsletter. Materials and Methods: Our investigation involved microbial remediation of Cr(VI without producing any byproduct. Bacterial cultures tolerating high concentrations of Cr were isolated from the soil sample collected from the chromite-contaminated sites of Sukinda, and their bioaccumulation properties were investigated. Strains capable of growing at 250 mg/L Cr(VI were considered as Cr resistant. Results: The experimental investigation showed the maximum specific Cr uptake at pH 7 and temperature 30oC. At about 50 mg/L initial Cr(VI concentrations, uptake of the selected potential strain exceeded 98% within 12 h of incubation. The bacterial isolate was identified by 16S rRNA sequencing as Brevebacterium casei. Conclusion: Results indicated promising approach for microbial remediation of effluents containing elevated levels of Cr(VI.

  15. Moss species benefits from breakdown of cyclic rodent dynamics in boreal forests.

    Science.gov (United States)

    Rydgren, Knut; Økland, Rune H; Picó, F Xavier; de Kroon, Hans

    2007-09-01

    Bryophytes have increased in abundance in northern regions, and climate changes have been proposed to account for this change. However, changes in the population dynamics of microtine rodents may also contribute to changes in bryophyte abundance. New evidence indicates a tendency for microtine rodent population oscillations to change from periodicity of 3-5 years to become irregular or acyclic. The impact on ecosystem functioning is potentially great. We study the impact of variation in microtine rodent population characteristics, such as cycle length and amplitude, on the population dynamics of the boreal, clonal moss Hylocomium splendens. We use experimental and observational demographic data to construct 127 scenarios representing all combinations of disturbance type (gap formation and/or clipping), period (cyclic with 4, 6, 12, or 24 years between rodent peaks; or acyclic with constant or stochastically varying annual disturbance severity) and disturbance severity (fraction of individuals affected by disturbance in each year relative to the maximum disturbance carried out in the field experiment; seven levels). Population data collected in the field during 13 years were used as a baseline scenario. By subjecting all scenarios to stochastic matrix modeling, we demonstrate considerable impact of microtine rodent on the population dynamics of H. splendens, most notably when rodent populations fluctuate with short periods and high peak disturbance severities. Under the same average disturbance severity, H. splendens population growth rates are highest in acyclic scenarios and are progressively reduced with increasing peak disturbance severities (i.e., with increasing period). Stochastic elasticity analyses show that in less variable environments mature segment survival contributes more to the population growth rate, while in more variable environments the regeneration pathway (branching of older parts of the plant) plays a stronger role, inevitably leading to lower

  16. Declines in large wildlife increase landscape-level prevalence of rodent-borne disease in Africa.

    Science.gov (United States)

    Young, Hillary S; Dirzo, Rodolfo; Helgen, Kristofer M; McCauley, Douglas J; Billeter, Sarah A; Kosoy, Michael Y; Osikowicz, Lynn M; Salkeld, Daniel J; Young, Truman P; Dittmar, Katharina

    2014-05-13

    Populations of large wildlife are declining on local and global scales. The impacts of this pulse of size-selective defaunation include cascading changes to smaller animals, particularly rodents, and alteration of many ecosystem processes and services, potentially involving changes to prevalence and transmission of zoonotic disease. Understanding linkages between biodiversity loss and zoonotic disease is important for both public health and nature conservation programs, and has been a source of much recent scientific debate. In the case of rodent-borne zoonoses, there is strong conceptual support, but limited empirical evidence, for the hypothesis that defaunation, the loss of large wildlife, increases zoonotic disease risk by directly or indirectly releasing controls on rodent density. We tested this hypothesis by experimentally excluding large wildlife from a savanna ecosystem in East Africa, and examining changes in prevalence and abundance of Bartonella spp. infection in rodents and their flea vectors. We found no effect of wildlife removal on per capita prevalence of Bartonella infection in either rodents or fleas. However, because rodent and, consequently, flea abundance doubled following experimental defaunation, the density of infected hosts and infected fleas was roughly twofold higher in sites where large wildlife was absent. Thus, defaunation represents an elevated risk in Bartonella transmission to humans (bartonellosis). Our results (i) provide experimental evidence of large wildlife defaunation increasing landscape-level disease prevalence, (ii) highlight the importance of susceptible host regulation pathways and host/vector density responses in biodiversity-disease relationships, and (iii) suggest that rodent-borne disease responses to large wildlife loss may represent an important context where this relationship is largely negative.

  17. Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities

    Directory of Open Access Journals (Sweden)

    Totta Ehret

    2017-06-01

    Full Text Available Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.

  18. The hip adductor muscle group in caviomorph rodents: anatomy and homology.

    Science.gov (United States)

    García-Esponda, César M; Candela, Adriana M

    2015-06-01

    Anatomical comparative studies including myological data of caviomorph rodents are relatively scarce, leading to a lack of use of muscular features in cladistic and morphofunctional analyses. In rodents, the hip adductor muscles constitute an important group of the hindlimb musculature, having an important function during the beginning of the stance phase. These muscles are subdivided in several distinct ways in the different clades of rodents, making the identification of their homologies hard to establish. In this contribution we provide a detailed description of the anatomical variation of the hip adductor muscle group of different genera of caviomorph rodents and identify the homologies of these muscles in the context of Rodentia. On this basis, we identify the characteristic pattern of the hip adductor muscles in Caviomorpha. Our results indicate that caviomorphs present a singular pattern of the hip adductor musculature that distinguishes them from other groups of rodents. They are characterized by having a single m. adductor brevis that includes solely its genicular part. This muscle, together with the m. gracilis, composes a muscular sheet that is medial to all other muscles of the hip adductor group. Both muscles probably have a synergistic action during locomotion, where the m. adductor brevis reinforces the multiple functions of the m. gracilis in caviomorphs. Mapping of analyzed myological characters in the context of Rodentia indicates that several features are recovered as potential synapomorphies of caviomorphs. Thus, analysis of the myological data described here adds to the current knowledge of caviomorph rodents from anatomical and functional points of view, indicating that this group has features that clearly differentiate them from other rodents.

  19. 7 CFR 58.147 - Insect and rodent control program.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Insect and rodent control program. 58.147 Section 58... Service 1 Operations and Operating Procedures § 58.147 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control...

  20. 7 CFR 58.247 - Insect and rodent control program.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Insect and rodent control program. 58.247 Section 58... Service 1 Operations and Operating Procedures § 58.247 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program...

  1. 20 CFR 654.415 - Insect and rodent control.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Insect and rodent control. 654.415 Section 654.415 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SPECIAL... Insect and rodent control. Housing and facilities shall be free of insects, rodents, and other vermin....

  2. Prevalence of leptospirosis and toxoplasmosis: A study of rodents ...

    African Journals Online (AJOL)

    Leptospira and Toxoplasma infections in rodents and shrews in Mikese area of Morogoro ... Human and other animals such as rodents excluding cats are intermediate hosts of ..... Berdoy, M., Webster, J.P. & Macdonald, D.W. (2000) Fatal attraction in rats ... Rats, Mice and People: Rodent Biology and Management, 543-547.

  3. Lawsonia intracellularis in the feces of wild rodents and stray cats captured around equine farms.

    Science.gov (United States)

    Hwang, Jeong-Min; Seo, Myung-Ji; Yeh, Jung-Yong

    2017-08-11

    Proliferative enteropathy is a global enteric disease of particular importance in pigs. The causative bacterium, Lawsonia intracellularis, has a wide range of susceptible host species. Recently, L. intracellularis has been recognized as an etiologic agent of an emerging enteric disease in foals called equine proliferative enteropathy (EPE). The presence of L. intracellularis in nonruminant wildlife has raised questions regarding the role of these species in EPE transmission. This study investigated exposure to L. intracellularis in wild rodents and feral cats from eight farms with confirmed EPE. Serum (42) and fecal (40) samples from resident foals and fecal samples (131), intestinal mucosa tissues (14), and mesenteric lymph nodes (14) from wild and feral animals were collected for the evaluation of the farm status and the molecular detection of L. intracellularis following the diagnosis of EPE in index cases. Fresh feces from wild rodents and feral cats were collected from the ground while walking the premises or after trapping the animals using live traps. A total of 3 brown rats, 7 house mice, 1 striped field mouse, 2 grey red-backed voles, and 3 feral cats showed evidence of prior exposure to L. intracellularis. Our data add to increasing evidence demonstrating the potential for L. intracellularis transmission and infection in wild rodents and feral cats and provide possible evidence of interspecies transmission. The exposure of wild rodents and feral cats provides potential evidence for the spillover of L. intracellularis to wildlife species and raises the question of spillback to horses. Additionally, these animals may represent an indicator of environmental exposure or may be actively involved in the transmission of L. intracellularis to foals by acting as potential reservoir/amplifier hosts. This study is the first to demonstrate the magnitude of L. intracellularis shedding in the feces of wild rodents and feral cats and to indicate the significant

  4. QSAR screening of 70,983 REACH substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the ChemScreen project

    DEFF Research Database (Denmark)

    Wedebye, Eva Bay; Dybdahl, Marianne; Nikolov, Nikolai Georgiev;

    2015-01-01

    for information requirements. As no testing for reproductive effects should be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for 70,983 REACH substances was performed. Sixteen models and three decision algorithms...... were used to reach overall predictions of substances with potential effects with the following result: 6.5% genotoxic carcinogens, 16.3% mutagens, 11.5% developmental toxicants. These results are similar to findings in earlier QSAR and experimental studies of chemical inventories, and illustrate how...... QSAR predictions may be used to identify potential genotoxic carcinogens, mutagens and developmental toxicants by high-throughput virtual screening....

  5. USE OF qRTPCR TO IDENTIFY POTENTIAL BIOMARKERS OF BROMATE EXPOSURE IN F344 MALE RAT KIDNEYS

    Science.gov (United States)

    Potassium bromate (KBrO3) is a drinking water disinfection by-product that is nephrotoxic and carcinogenic. To identify potential biomarkers of carcinogenicity, male F344 rats were chronically exposed to a carcinogenic dose (400mg/l) of KBrO3 in their drinking water. Kidneys were...

  6. A Theoretical Approach to Relate the Reactivity Descriptors and Mulliken Charges with Carcinogenity of Some Methylated Benzo[a]Anthracene

    Directory of Open Access Journals (Sweden)

    Mahmoud S. Said

    2012-06-01

    Full Text Available Quantum chemical calculations were carried out to explain how the electronic state and reactivity indices of some methylated benzo [a] anthracenes vary with position and number of methyl substituent in molecules. The global reactivity descriptors such as ionization energy, electron affinity, molecular hardness, chemical potential and molecular philicity were estimated at ab-initio level of theory employing HF /3-21G basis set. After that these factors were correlated with the carcinogenic activity of these compounds. The result showed that two of these factors (The ionization potential (IP and the total charge at K & L regions can be correlated with carcinogenic activity of these compounds. On the other hand we found that methyl substitution leads to a great variation on the Mulliken charge of the carbon atoms at and near to the methyl substituents.

  7. Acrylamide-induced carcinogenicity in mouse lung involves mutagenicity: cII gene mutations in the lung of big blue mice exposed to acrylamide and glycidamide for up to 4 weeks.

    Science.gov (United States)

    Manjanatha, Mugimane G; Guo, Li-Wu; Shelton, Sharon D; Doerge, Daniel R

    2015-06-01

    Potential health risks for humans from exposure to acrylamide (AA) and its epoxide metabolite glycidamide (GA) have garnered much attention lately because substantial amounts of AA are present in a variety of fried and baked starchy foods. AA is tumorigenic in rodents, and a large number of in vitro and in vivo studies indicate that AA is genotoxic. A recent cancer bioassay on AA demonstrated that the lung was one of the target organs for tumor induction in mice; however, the mutagenicity of AA in this tissue is unclear. Therefore, to investigate whether or not gene mutation is involved in the etiology of AA- or GA-induced mouse lung carcinogenicity, we screened for cII mutant frequency (MF) in lungs from male and female Big Blue (BB) mice administered 0, 1.4, and 7.0 mM AA or GA in drinking water for up to 4 weeks (19-111 mg/kg bw/days). Both doses of AA and GA produced significant increases in cII MFs, with the high doses producing responses 2.7-5.6-fold higher than the corresponding controls (P ≤ 0.05; control MFs = 17.2 ± 2.2 and 15.8 ± 3.5 × 10(-6) in males and females, respectively). Molecular analysis of the mutants from high doses indicated that AA and GA produced similar mutation spectra and that these spectra were significantly different from the spectra in control mice (P ≤ 0.01). The predominant types of mutations in the lung cII gene from AA- and GA-treated mice were A:T → T:A, and G:C → C:G transversions, and -1/+1 frameshifts at a homopolymeric run of Gs. The MFs and types of mutations induced by AA and GA in the lung are consistent with AA exerting its genotoxicity via metabolism to GA. These results suggest that AA is a mutagenic carcinogen in mouse lungs and therefore further studies on its potential health risk to humans are warranted. Environ. Mol. Mutagen. 56:446-456, 2015. © 2015 Wiley Periodicals, Inc.

  8. Genotyping and subtyping of Giardia and Cryptosporidium isolates from commensal rodents in China.

    Science.gov (United States)

    Zhao, Z; Wang, R; Zhao, W; Qi, M; Zhao, J; Zhang, L; Li, J; Liu, A

    2015-05-01

    Cryptosporidium and Giardia are two important zoonotic intestinal parasites responsible for diarrhoea in humans and other animals worldwide. Rodents, as reservoirs or carriers of Cryptosporidium and Giardia, are abundant and globally widespread. In the present study, we collected 232 fecal specimens from commensal rodents captured in animal farms and farm neighbourhoods in China. We collected 33 Asian house rats, 168 brown rats and 31 house mice. 6.0% (14/232) and 8.2% (19/232) of these rodents were microscopy-positive for Giardia cysts and Cryptosporidium oocysts, respectively. All 14 Giardia isolates were identified as Giardia duodenalis assemblage G at a minimum of one or maximum of three gene loci (tpi, gdh and bg). By small subunit rRNA (SSU rRNA) gene sequencing, Cryptosporidium parvum (n = 12) and Cryptosporidium muris (n = 7) were identified. The gp60 gene encoding the 60-kDa glycoprotein was successfully amplified and sequenced in nine C. parvum isolates, all of which belonged to the IIdA15G1 subtype. Observation of the same IIdA15G1 subtype in humans (previously) and in rodents (here) suggests that rodents infected with Cryptosporidium have the potential to transmit cryptosporidiosis to humans.

  9. Preliminary molecular characterization of Cryptosporidium parvum isolates of wildlife rodents from Poland.

    Science.gov (United States)

    Bajer, A; Cacciò, S; Bednarska, M; Behnke, J M; Pieniazek, N J; Sinski, E

    2003-10-01

    Isolates of Cryptosporidium were collected from 3 species of woodland and field rodents (Clethrionomys glareolus, Microtus arvalis, and Apodemus flavicollis) and were characterized by polymerase chain reaction amplification and sequencing of fragments of the oocyst wall protein (COWP) gene and of the 18S ribosomal RNA gene. Sequence analysis of these markers revealed that the animals were infected with C. parvum, and that the genotype involved was almost identical to the mouse genotype previously described from Mus musculus. Thus, small rodents should be considered as an important reservoir of C. parvum genotypes closely related to the zoonotic genotype 2 and potentially hazardous to humans.

  10. An analysis of the Gene-Tox Carcinogen Data Base.

    Science.gov (United States)

    Nesnow, S; Bergman, H

    1988-01-01

    The Gene-Tox Carcinogen Data Base is an evaluated source of cancer data on 506 chemicals selected in part for their previous assessment in genetic toxicology bioassays. This data base has been analyzed for the distribution of these chemicals into chemical classes. The major chemical classes (6% or greater of the total data base) are: acyl-, alkyl-, and aryl-halides; alcohols and phenols; aliphatic and aromatic amines, amides, and sulfonamides; benzene-ring-containing chemicals; organo-lead, -mercury, -phosphorous compounds, metals and derivatives, phosphoric acid esters, and phosphoramides; and polycyclic aromatic hydrocarbons. Cancer studies representing a subset of the Gene-Tox Carcinogen Data Base, 199 chemicals which were rated as Sufficient Positive/Negative or Limited Positive/Negative, were examined for distribution of those studies by animal species, gender, route of chemical administration, duration of study, major tumor sites, and major tumor types. These analyses revealed that the Gene-Tox Carcinogen Data Base contains a large number of lifetime studies involving the rat and mouse treated by oral routes of administration. The major organs that were targets were: liver, lung, skin, forestomach, bladder, and mammary gland, while the major tumor types were: carcinoma, sarcoma, papilloma, and adenoma. Chemicals in the data base have been assessed for species-specific carcinogenic effects, and these results indicate that for mice and rats there is a high correspondence (85%). This number is higher than that (71%) reported by Tennant et al. (1986) based on the recent results of 72 chronic cancer bioassays performed by the National Toxicology Program. This difference is probably based on the nature of the chemicals selected for inclusion in both data bases. Although the absolute value of this correspondence is unknown, it would seem to be within this range. When chemicals in the Gene-Tox Carcinogen Data Base were examined for their previous evaluation in 73

  11. The influence of the cage environment on rodent physiology and behavior: Implications for reproducibility of pre-clinical rodent research.

    Science.gov (United States)

    Toth, Linda A

    2015-08-01

    The reproducibility of pre-clinical research is an important concern that is now being voiced by constituencies that include the National Institutes of Health, the pharmaceutical industry, Congress, the public and the scientific community. An important facet of performing and publishing well-controlled reproducible pre-clinical research is to stabilize and more completely define the environment of the animal subjects. Scientists who use rodents in research generally recognize the importance of maintaining a stable animal environment. However, despite a theoretical and general awareness of these issues, many may lack a true appreciation of how significantly even seemingly minor variations in the environment can affect research outcomes. The purpose of this article is to help investigators gain a more comprehensive and substantiated understanding of the potentially significant impact of even seemingly minor environmental changes on the animals and the data. An important caveat to this article is that the examples presented were selected from a very large literature, admittedly in order to illustrate certain points. The goal of this article is not to provide an overview of the entire literature on how the environment affects rodents but rather to make preclinical scientists more aware of how these factors can potentially influence the experimental data and contribute to poor reproducibility of research. Copyright © 2015. Published by Elsevier Inc.

  12. Biodegradation of carcinogenic textile azo dyes using bacterial isolates of mangrove sediment

    Directory of Open Access Journals (Sweden)

    Guru Prasad Srinivasan

    2014-02-01

    Full Text Available Objective: To evaluate the biodegrading property against carcinogenic azo dyes using bacterial isolates of mangrove sediment. Methods: The bacterial isolates were subjected to submerged fermentation and their growth kinetics were studied. The potential strain was characterized using 16S rDNA sequencing. Results: In the present study, dye degrading bacterial colonies were isolated from the mangrove sediment samples of Parangipettai estuarine area, Tamil Nadu. Of the 30 morphologically different strains isolated, 5 showed antagonistic property. The growth kinetics of the two strains, P1 and G1, which showed potent activity were calculated. One particular isolate (P1 showing promising dye degrading potential in the submerged fermentation was further characterized. The strain was identified as Paenibacillus sp. by 16S rDNA sequencing. Conclusions: This study reveals the less explored microflora of mangrove sediments. The novel strain may further be analyzed and used in the treatment of effluent from dye industry so as to reduce the impact of carcinogenic contaminants.

  13. Biodegradation of carcinogenic textile azo dyes using bacterial isolates of mangrove sediment

    Institute of Scientific and Technical Information of China (English)

    Guru Prasad Srinivasan; Asnar Sikkanthar; Anandajothi Elamaran; Caroline R Delma; Kumaran Subramaniyan

    2014-01-01

    Objective:To evaluate the biodegrading property against carcinogenic azo dyes using bacterial isolates of mangrove sediment. Methods: The bacterial isolates were subjected to submerged fermentation and their growth kinetics were studied. The potential strain was characterized using 16S rDNA sequencing. Results:In the present study, dye degrading bacterial colonies were isolated from the mangrove sediment samples of Parangipettai estuarine area, Tamil Nadu. Of the 30 morphologically different strains isolated, 5 showed antagonistic property. The growth kinetics of the two strains, P1 and G1, which showed potent activity were calculated. One particular isolate (P1) showing promising dye degrading potential in the submerged fermentation was further characterized. The strain was identified as Paenibacillus sp. by 16S rDNA sequencing. Conclusions:This study reveals the less explored microflora of mangrove sediments. The novel strain may further be analyzed and used in the treatment of effluent from dye industry so as to reduce the impact of carcinogenic contaminants.

  14. Evaluation of carcinogenic hazard of diesel engine exhaust needs to consider revolutionary changes in diesel technology.

    Science.gov (United States)

    McClellan, Roger O; Hesterberg, Thomas W; Wall, John C

    2012-07-01

    Diesel engines, a special type of internal combustion engine, use heat of compression, rather than electric spark, to ignite hydrocarbon fuels injected into the combustion chamber. Diesel engines have high thermal efficiency and thus, high fuel efficiency. They are widely used in commerce prompting continuous improvement in diesel engines and fuels. Concern for health effects from exposure to diesel exhaust arose in the mid-1900s and stimulated development of emissions regulations and research to improve the technology and characterize potential health hazards. This included epidemiological, controlled human exposure, laboratory animal and mechanistic studies to evaluate potential hazards of whole diesel exhaust. The International Agency for Research on Cancer (1989) classified whole diesel exhaust as - "probably carcinogenic to humans". This classification stimulated even more stringent regulations for particulate matter that required further technological developments. These included improved engine control, improved fuel injection system, enhanced exhaust cooling, use of ultra low sulfur fuel, wall-flow high-efficiency exhaust particulate filters, exhaust catalysts, and crankcase ventilation filtration. The composition of New Technology Diesel Exhaust (NTDE) is qualitatively different and the concentrations of particulate constituents are more than 90% lower than for Traditional Diesel Exhaust (TDE). We recommend that future reviews of carcinogenic hazards of diesel exhaust evaluate NTDE separately from TDE.

  15. Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation.

    Science.gov (United States)

    Afshari, C A; Nuwaysir, E F; Barrett, J C

    1999-10-01

    One major challenge facing today's cancer researchers and toxicologists is the development of new approaches for the identification of carcinogens and other environmental hazards. Here, we describe the potential impact of emerging technologies for measuring gene expression profiles on carcinogen identification and on the general field of toxicology. An example of one of these technologies is the use of cDNA microarray chips. We provide an overview to the key questions that are confronting investigators charged with determining the relative safety of natural or synthetic chemicals to which humans are exposed, followed by a discussion of how cDNA microarray technology may be applied to these questions. Gene chip technology is still a relatively new technology, and only a handful of studies have demonstrated its utility. However, as the technical hurdles to development are passed, the use of this methodology in addressing the questions raised here will be critical to increase the sensitivity of detection of the potential toxic effects of environmental chemicals and to understand their risks to humans.

  16. /sup 32/P-Postlabeling test for covalent DNA binding of chemicals in vivo: Application to a variety of aromatic carcinogens and methylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, M.V.; Gupta, R.C.; Randerath, E.; Randerath, K.

    1984-02-01

    Carcinogen--DNA adducts were detected and determined by /sup 32/P-postlabeling assay after exposure of mouse or rat tissues in vivo to a total of 28 compounds comprising 7 arylamines and derivatives, 3 azo compounds, 2 nitroaromatics, 12 polycyclic aromatic hydrocarbons, and 4 methylating agents. DNA was isolated from mouse skin, mouse liver, and rat liver after treatment with the individual carcinogens, then digested enzymatically to deoxyribonucleoside 3'-monophosphates, which were converted to 5'-/sup 32/P-labeled deoxyribonucleoside 3',5'-bisphosphates by T4 polynucleotide kinase-catalyzed (/sup 32/P)phosphate transfer from (gamma-/sup 32/P)ATP. The nucleotides were resolved by anion-exchange t.l.c. on polyethyleneimine-cellulose and detected by autoradiography. The determination of low levels of DNA binding of the aromatic carcinogens entailed the removal of normal nucleotides prior to the resolution of adduct nucleotides. For this purpose, an alternative procedure employing reversed-phase t.l.c. was devised which offered advantages for the detection of quantitatively minor adducts. The procedures described enabled the detection of 1 aromatic DNA adduct in approximately 10(/sup 8/) normal nucleotides, while the limit of detection of methylated adducts was 1 adduct in approximately 6 X 10(/sup 5/) nucleotides. The results show that a great number of carcinogen-DNA adducts of diverse structure are substrates for /sup 32/P-labeling by polynucleotide kinase-catalyzed phosphorylation. Because covalent DNA adduct formation in vivo appears to be an essential property of the majority of chemical carcinogens, /sup 32/P-postlabeling analysis of carcinogen--DNA adducts in mammalian tissues may serve as a test for the screening of chemicals for potential carcinogenicity.

  17. Excitatory GABA in rodent developing neocortex in vitro.

    Science.gov (United States)

    Rheims, Sylvain; Minlebaev, Marat; Ivanov, Anton; Represa, Alfonso; Khazipov, Rustem; Holmes, Gregory L; Ben-Ari, Yehezkel; Zilberter, Yuri

    2008-08-01

    GABA depolarizes immature cortical neurons. However, whether GABA excites immature neocortical neurons and drives network oscillations as in other brain structures remains controversial. Excitatory actions of GABA depend on three fundamental parameters: the resting membrane potential (Em), reversal potential of GABA (E(GABA)), and threshold of action potential generation (Vthr). We have shown recently that conventional invasive recording techniques provide an erroneous estimation of these parameters in immature neurons. In this study, we used noninvasive single N-methyl-d-aspartate and GABA channel recordings in rodent brain slices to measure both Em and E(GABA) in the same neuron. We show that GABA strongly depolarizes pyramidal neurons and interneurons in both deep and superficial layers of the immature neocortex (P2-P10). However, GABA generates action potentials in layer 5/6 (L5/6) but not L2/3 pyramidal cells, since L5/6 pyramidal cells have more depolarized resting potentials and more hyperpolarized Vthr. The excitatory GABA transiently drives oscillations generated by L5/6 pyramidal cells and interneurons during development (P5-P12). The NKCC1 co-transporter antagonist bumetanide strongly reduces [Cl(-)]i, GABA-induced depolarization, and network oscillations, confirming the importance of GABA signaling. Thus a strong GABA excitatory drive coupled with high intrinsic excitability of L5/6 pyramidal neurons and interneurons provide a powerful mechanism of synapse-driven oscillatory activity in the rodent neocortex in vitro. In the companion paper, we show that the excitatory GABA drives layer-specific seizures in the immature neocortex.

  18. Multisite carcinogenicity and respiratory toxicity of inhaled 1-bromopropane in rats and mice.

    Science.gov (United States)

    Morgan, Daniel L; Nyska, Abraham; Harbo, Sam Jens; Grumbein, Sondra L; Dill, Jeffrey A; Roycroft, Joseph H; Kissling, Grace E; Cesta, Mark F

    2011-10-01

    Two-year 1-bromopropane (1-BP) inhalation studies were conducted because of the potential for widespread exposure, the lack of chronic toxicity and carcinogenicity data, and the known carcinogenicity of structurally related compounds. Male and female F344/N rats and B6C3F1/N mice were exposed by inhalation to 0, 62.5 (mice only), 125, 250, or 500 (rats only) ppm 1-BP for 6 hr/day, 5 days/week for 105 weeks. Exposure of male and female rats to 1-BP resulted in significantly increased incidences of adenomas of the large intestine and skin neoplasms. In male rats, the incidence of malignant mesothelioma of the epididymis was statistically significantly increased at 500 ppm, but the biological significance of this common lesion is unclear. Incidences of pancreatic islet adenoma in male rats were significantly increased at all concentrations relative to concurrent controls but were within the historical control range for inhalation studies. There was no evidence of carcinogenic activity of 1-BP in male B6C3F1 mice; however, significantly increased incidences of alveolar/bronchiolar neoplasms of the lung were present in female mice. Exposure to 1-BP also resulted in increased incidences of nonneoplastic lesions in the nose of rats and mice, the larynx of rats and male mice, the trachea of female rats and male and female mice, and the lungs of mice. Inflammatory lesions with Splendore Hoeppli (S-H) material were present primarily in the nose and skin of exposed male and female rats, indicating that 1-BP caused immunosuppression.

  19. The function and significance of SELENBP1 downregulation in human bronchial epithelial carcinogenic process.

    Directory of Open Access Journals (Sweden)

    Gu-Qing Zeng

    Full Text Available BACKGROUND: Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1 was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC carcinogenesis. METHODS: iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(apyrene (B[a]P-induced human bronchial epithelial cell transformation were determined. RESULTS: 102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. CONCLUSIONS: The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.

  20. Perinatal Toxicity and Carcinogenicity Studies of Styrene –Acrylonitrile Trimer, A Ground Water Contaminant

    Science.gov (United States)

    Behl, Mamta; Elmore, Susan A.; Malarkey, David E.; Hejtmancik, Milton R.; Gerken, Diane K.; Chhabra, Rajendra S.

    2015-01-01

    Styrene Acrylonitrile (SAN) Trimer is a by-product in the production of acrylonitrile styrene plastics. Following a report of a childhood cancer cluster in the Toms River section of Dover Township, New Jersey, SAN Trimer was identified as one of the groundwater contaminants at Reich Farm Superfund site in the township. The contaminants from the Reich Farm site’s ground water plume impacted two wells at the Parkway well field. The National Toxicology Program (NTP) studied the toxicity and carcinogenicity of SAN Trimer in rats exposed during their perinatal developmental period and adulthood. The chronic toxicity and carcinogenicity studies in F344/N rats were preceded by 7- and 18-week perinatal toxicity studies to determine the exposure concentrations for the 2-year studies. Subsequently, Fisher 344 pregnant dams were exposed to SAN Trimer containing diet at 400, 800, or 1600 ppm concentrations during gestation, nursing and weaning periods of offspring followed by two year of adult exposures to both male and female pups. There was no statistically significant evidence of carcinogenic activity following SAN-Trimer exposure; however, rare neoplasms in the brain and spinal cord were observed in males and to lesser extent in female rats. These incidences were considered within the range of historical background in the animal model used in the current studies. Therefore, the presence of a few rarely occurring CNS tumors in the treated groups were not judged to be associated with the SAN Trimer exposure. The major finding was a dose-related peripheral neuropathy associated with the sciatic nerves in females and spinal nerve roots in males and females thereby suggesting that SAN trimer is potentially a nervous system toxicant. PMID:24060431

  1. Perinatal toxicity and carcinogenicity studies of styrene-acrylonitrile trimer, a ground water contaminant.

    Science.gov (United States)

    Behl, Mamta; Elmore, Susan A; Malarkey, David E; Hejtmancik, Milton R; Gerken, Diane K; Chhabra, Rajendra S

    2013-12-06

    Styrene acrylonitrile (SAN) trimer is a by-product in the production of acrylonitrile styrene plastics. Following a report of a childhood cancer cluster in the Toms River section of Dover Township, New Jersey, SAN Trimer was identified as one of the groundwater contaminants at Reich Farm Superfund site in the township. The contaminants from the Reich Farm site's ground water plume impacted two wells at the Parkway well field. The National Toxicology Program (NTP) studied the toxicity and carcinogenicity of SAN Trimer in rats exposed during their perinatal developmental period and adulthood. The chronic toxicity and carcinogenicity studies in F344/N rats were preceded by 7- and 18-week perinatal toxicity studies to determine the exposure concentrations for the 2-year studies. Subsequently, Fisher 344 pregnant dams were exposed to SAN Trimer containing diet at 400, 800, or 1600ppm concentrations during gestation, nursing and weaning periods of offspring followed by two year of adult exposures to both male and female pups. There was no statistically significant evidence of carcinogenic activity following SAN-Trimer exposure; however, rare neoplasms in the brain and spinal cord were observed in males and to lesser extent in female rats. These incidences were considered within the range of historical background in the animal model used in the current studies. Therefore, the presence of a few rarely occurring CNS tumors in the treated groups were not judged to be associated with the SAN Trimer exposure. The major finding was a dose-related peripheral neuropathy associated with the sciatic nerves in females and spinal nerve roots in males and females thereby suggesting that SAN Trimer is potentially a nervous system toxicant.

  2. Aflatoxins in Iran: Nature, Hazards and Carcinogenicity

    Directory of Open Access Journals (Sweden)

    DD Farhud

    2011-12-01

    Full Text Available Many studies have shown that mycotoxin contamination of agricultural products is a challenge for individual's health espe­cially in developing countries. Improper production and storage of foods, prepare conditions for aflatoxin production in crops, especially rice, wheat, pistachio, walnut, almond, etc which are the main sources of foods for people. Feeding live­stock by contaminated bread is another way of human exposure to mycotoxins, especially aflatoxin and because of expen­sive methods for detecting and analyzing aflatoxin in laboratory; it is not measured in foods. This manuscript is a review of some Iranian and nonIranian reports about aflatoxin, its exposure ways, its adverse effect on human health and nutrition, as well as methods for reducing its exposure. Based on studies on foods, aflatoxin exposure is high in Iran. Since livestock feeding by contaminated bread is one of the potential ways for milk contamination, we should control and reduce aflatoxin contamination by improving production process, storage condition and livestock feeding as soon as possible. Pistachio is one of the most important exporting products of Iran and to maintain Iran's position in exporting of this product, specific regulations on lowering its contamination with aflatoxin should be considered seriously. Finally, effective controlling of all food and feedstuffs which are vulnerable to aflatoxin contamination is necessary to prevent its effects.

  3. Rehabilitative Soft Exoskeleton for Rodents.

    Science.gov (United States)

    Florez, Juan Manuel; Shah, Manan; Moraud, Eduardo Martin; Wurth, Sophie; Baud, Laetitia; Von Zitzewitz, Joachim; van den Brand, Rubia; Micera, Silvestro; Courtine, Gregoire; Paik, Jamie

    2017-02-01

    Robotic exoskeletons provide programmable, consistent and controllable active therapeutic assistance to patients with neurological disorders. Here we introduce a prototype and preliminary experimental evaluation of a rehabilitative gait exoskeleton that enables compliant yet effective manipulation of the fragile limbs of rats. To assist the displacements of the lower limbs without impeding natural gait movements, we designed and fabricated soft pneumatic actuators (SPAs). The exoskeleton integrates two customizable SPAs that are attached to a limb. This configuration enables a 1 N force load, a range of motion exceeding 80 mm in the major axis, and speed of actuation reaching two gait cycles/s. Preliminary experiments in rats with spinal cord injury validated the basic features of the exoskeleton. We propose strategies to improve the performance of the robot and discuss the potential of SPAs for the design of other wearable interfaces.

  4. A study of the carcinogenicity of glycidol in Syrian hamsters.

    Science.gov (United States)

    Lijinsky, W; Kovatch, R M

    1992-01-01

    The industrial chemical glycidol is a directly acting mutagen and a broadly acting carcinogen in rats. It was administered to Syrian golden hamsters (20 male and 20 female) by gavage of 12 mg twice a week for 60 weeks. The total dose per animal was 1.45 g or 20 mmol. Survival was not different from control hamsters treated with corn oil/ethyl acetate. Of the treated males, 9 had tumors and 13 of the treated females had tumors, some of which were adrenal cortex tumors seen in controls. More tumors were seen in the glycidol-treated hamsters than in controls, but the spleen was the only notable target organ and the number of animals with spleen hemangiosarcomas was small. Glycidol appeared to be less carcinogenic in hamsters than in rats or mice.

  5. 4-Dimethylaminoazobenzenes: carcinogenicities and reductive cleavage by microsomal azo reductase.

    Science.gov (United States)

    Lambooy, J P; Koffman, B M

    1985-01-01

    Twenty-four 4-dimethylaminoazobenzenes (DABs) in which systematic structural modifications have been made in the prime ring have been studied for substrate specificity for microsomal azo reductase. The DABs were also evaluated for carcinogenicity and it was found that there was no correlation between carcinogenicity and extent of azo bond cleavage by azo reductase. While any substituent in the prime ring reduces the rate of cleavage of the azo bond relative to the unsubstituted dye, there is a correlation between substituent size and susceptibility to the enzyme. Substituent size was also found to be a significant factor in the induction of hepatomas by the dyes. Preliminary studies have shown that there appears to be a positive correlation between microsomal riboflavin content and the activity of the azo reductase.

  6. Association of Bartonella Species with Wild and Synanthropic Rodents in Different Brazilian Biomes.

    Science.gov (United States)

    Gonçalves, Luiz Ricardo; Favacho, Alexsandra Rodrigues de Mendonça; Roque, André Luiz Rodrigues; Mendes, Natalia Serra; Fidelis Junior, Otávio Luiz; Benevenute, Jyan Lucas; Herrera, Heitor Miraglia; D'Andrea, Paulo Sérgio; de Lemos, Elba Regina Sampaio; Machado, Rosangela Zacarias; André, Marcos Rogério

    2016-12-15

    Bartonella spp. comprise an ecologically successful group of microorganisms that infect erythrocytes and have adapted to different hosts, which include a wide range of mammals, besides humans. Rodents are reservoirs of about two-thirds of Bartonella spp. described to date; and some of them have been implicated as causative agents of human diseases. In our study, we performed molecular and phylogenetic analyses of Bartonella spp. infecting wild rodents from five different Brazilian biomes. In order to characterize the genetic diversity of Bartonella spp., we performed a robust analysis based on three target genes, followed by sequencing, Bayesian inference, and maximum likelihood analysis. Bartonella spp. were detected in 25.6% (117/457) of rodent spleen samples analyzed, and this occurrence varied among different biomes. The diversity analysis of gltA sequences showed the presence of 15 different haplotypes. Analysis of the phylogenetic relationship of gltA sequences performed by Bayesian inference and maximum likelihood showed that the Bartonella species detected in rodents from Brazil was closely related to the phylogenetic group A detected in other cricetid rodents from North America, probably constituting only one species. Last, the Bartonella species genogroup identified in the present study formed a monophyletic group that included Bartonella samples from seven different rodent species distributed in three distinct biomes. In conclusion, our study showed that the occurrence of Bartonella bacteria in rodents is much more frequent and widespread than previously recognized. In the present study, we reported the occurrence of Bartonella spp. in some sites in Brazil. The identification and understanding of the distribution of this important group of bacteria may allow the Brazilian authorities to recognize potential regions with the risk of transmission of these pathogens among wild and domestic animals and humans. In addition, our study accessed important gaps in

  7. Molecular epidemiology of paramyxoviruses in Zambian wild rodents and shrews.

    Science.gov (United States)

    Sasaki, Michihito; Muleya, Walter; Ishii, Akihiro; Orba, Yasuko; Hang'ombe, Bernard M; Mweene, Aaron S; Moonga, Ladslav; Thomas, Yuka; Kimura, Takashi; Sawa, Hirofumi

    2014-02-01

    Rodents and shrews are known to harbour various viruses. Paramyxoviruses have been isolated from Asian and Australian rodents, but little is known about them in African rodents. Recently, previously unknown paramyxovirus sequences were found in South African rodents. To date, there have been no reports related to the presence and prevalence of paramyxoviruses in shrews. We found a high prevalence of paramyxoviruses in wild rodents and shrews from Zambia. Semi-nested reverse transcription-PCR assays were used to detect paramyxovirus RNA in 21 % (96/462) of specimens analysed. Phylogenetic analysis revealed that these viruses were novel paramyxoviruses and could be classified as morbillivirus- and henipavirus-related viruses, and previously identified rodent paramyxovirus-related viruses. Our findings suggest the circulation of previously unknown paramyxoviruses in African rodents and shrews, and provide new information regarding the geographical distribution and genetic diversity of paramyxoviruses.

  8. The Role of Tobacco-Derived Carcinogens in Pancreas Cancer

    OpenAIRE

    Lochan, Rajiv; Reeves, Helen L.; Daly, Anne K.; Charnley, Richard M

    2011-01-01

    The extremely poor outcome from pancreas cancer is well known. However, its aetiology less well appreciated, and the molecular mechanisms underlying this are poorly understood. Tobacco usage is one of the strongest risk factors for this disease, and this is a completely avoidable hazard. In addition, there are well described hereditary diseases which predispose, and familial pancreas cancer. We have sought here to summarise the role of tobacco-derived carcinogens and the mode of their tumorig...

  9. Dose-response relationships for carcinogens: a review.

    OpenAIRE

    Zeise, L; Wilson, R.; Crouch, E A

    1987-01-01

    We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinea...

  10. Overview of bioassays for mutagens, carcinogens, and teratogens

    Energy Technology Data Exchange (ETDEWEB)

    Dumont, J.N.

    1982-01-01

    Bioassays to determine the risk of health hazards of man-made chemical substances are reviewed. The standard approach to testing a substance is the tier system, consisting of three levels of testing that are increasingly complex, lengthy, and costly. The paper describes the biological basis of bioassays, identifies various assays for mutagens, carcinogens and teratogens, and explains the problems involved in extrapolating test data to human risk estimates. Future improvements in assay techniques are discussed. (CR)

  11. Rodent reservoirs of future zoonotic diseases.

    Science.gov (United States)

    Han, Barbara A; Schmidt, John Paul; Bowden, Sarah E; Drake, John M

    2015-06-02

    The increasing frequency of zoonotic disease events underscores a need to develop forecasting tools toward a more preemptive approach to outbreak investigation. We apply machine learning to data describing the traits and zoonotic pathogen diversity of the most speciose group of mammals, the rodents, which also comprise a disproportionate number of zoonotic disease reservoirs. Our models predict reservoir status in this group with over 90% accuracy, identifying species with high probabilities of harboring undiscovered zoonotic pathogens based on trait profiles that may serve as rules of thumb to distinguish reservoirs from nonreservoir species. Key predictors of zoonotic reservoirs include biogeographical properties, such as range size, as well as intrinsic host traits associated with lifetime reproductive output. Predicted hotspots of novel rodent reservoir diversity occur in the Middle East and Central Asia and the Midwestern United States.

  12. Bats and Rodents Shape Mammalian Retroviral Phylogeny.

    Science.gov (United States)

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-11-09

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general.

  13. Homeobox Genes in the Rodent Pineal Gland

    DEFF Research Database (Denmark)

    Rath, Martin Fredensborg; Rohde, Kristian; Klein, David C

    2013-01-01

    The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential...... for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental...... functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function...

  14. Detection and characterization of a novel polyomavirus in wild rodents.

    Science.gov (United States)

    Orba, Yasuko; Kobayashi, Shintaro; Nakamura, Ichiro; Ishii, Akihiro; Hang'ombe, Bernard M; Mweene, Aaron S; Thomas, Yuka; Kimura, Takashi; Sawa, Hirofumi

    2011-04-01

    To investigate polyomavirus infection in wild rodents, we analysed DNA samples from the spleens of 100 wild rodents from Zambia using a broad-spectrum PCR-based assay. A previously unknown polyomavirus genome was identified in a sample from a multimammate mouse (Mastomys species) and the entire viral genome of 4899 bp was subsequently sequenced. This viral genome contained potential ORFs for the capsid proteins, VP1, VP2 and VP3, and early proteins, small t antigen and large T antigen. Phylogenetic analysis showed that it was a novel member of the family Polyomaviridae, and thus the virus was tentatively named mastomys polyomavirus. After transfection of the viral genome into several mammalian cell lines, transient expression of the VP1 and large T antigen proteins was confirmed by immunoblotting and immunocytochemical analyses. Comparison of large T antigen function in mastomys polyomavirus with that in rhesus monkey polyomavirus SV40 and human polyomavirus JC virus revealed that the large T antigen from mastomys polyomavirus interacted with the tumour suppressor protein pRb, but not with p53.

  15. Workplace carcinogen and pesticide exposures in Costa Rica.

    Science.gov (United States)

    Partanen, Timo; Chaves, Jorge; Wesseling, Catharina; Chaverri, Fabio; Monge, Patricia; Ruepert, Clemens; Aragón, Aurora; Kogevinas, Manolis; Hogstedt, Christer; Kauppinen, Timo

    2003-01-01

    The CAREX data system converts national workforce volumes and proportions of workers exposed to workplace carcinogens into numbers of exposed in 55 industrial categories. CAREX was adapted for Costa Rica for 27 carcinogens and seven groups of pesticides. Widespread workplace carcinogens in the 1.3 million workforce of Costa Rica are solar radiation (333,000 workers), diesel engine exhaust (278,000), environmental tobacco smoke (71,000), hexavalent chromium compounds (55,000), benzene (52,000), wood dust (32,000), silica dust (27,000), lead and inorganic lead compounds (19,000), and polycyclic aromatic compounds (17,000). The most ubiquitous pesticides were paraquat and diquat (175,000), mancozeb, maneb, and zineb (49,000), chlorothalonil (38,000), benomyl (19,000), and chlorophenoxy herbicides (11,000). Among women, formaldehyde, radon, and methylene chloride overrode pesticides, chromium, wood dust, and silica dust in numbers of exposed. High-risk sectors included agriculture, construction, personal and household services, land and water transport and allied services, pottery and similar industries, woodworks, mining, forestry and logging, fishing, manufacturing of electrical machinery, and bar and restaurant personnel.

  16. Linearity of dose-response relationships for human carcinogenic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.H. (Univ. of California, Berkeley (USA))

    The shape of dose-response relationships is a critical factor in considering cancer risks for the work place and environmental exposure to carcinogens. Markedly different risk estimates result from assumptions of linearity versus sublinear and threshold assumptions. This paper presents evidence that the relationship between the relative risk of development of cancer and the dose rate to carcinogenic exposures is frequently linear with no evidence for thresholds. Dose-response relationships from four studies of asbestos and lung cancer were examined, all of which were consistent with a linear relationship. Analysis of the relationship between the relative risk of lung cancer and exposure to nickel in a smelter study, selected because of relatively good exposure data, demonstrated a close agreement with a linear relationship. The relationship between the level of arsenic in drinking wter and the prevalence of skin cancer also was linear for males in the highest prevalence age group in Taiwan, although there was some evidence of sublinearity for females and younger persons. Also, the relationships between the number of cigarettes smoked per day and the relative risk of lung cancer was very close to linear in many studies. The analysis of these and other studies involving human exposure to carcinogens provides empirical evidence for linearity when the response variable is a rate ratio measure, rather than a risk difference measure. Linearity in dose-response is biologically plausible, without invoking a one-hit model. Except in special circumstances. the epidemiological evidence supports linear extrapolation of cancer relative risks.

  17. Chemotherapy of Rodent Malaria. Part 1.

    Science.gov (United States)

    1986-09-01

    nave bene’o rried out and talc screeningisr- -x , -doj to all of te s rainz of rodent malaria held in our A : ,-W ",2h5ni q uV wn i .’n re. .,cenLI y...hepitocytes. After two hours incubation, 1 ml of MEM with ’C, anti biotics and cortisone is added to each of the ,t re . r,,,-,I r o t o i *!.,1r- S 1- a :I

  18. Evidence for novel hepaciviruses in rodents.

    Directory of Open Access Journals (Sweden)

    Jan Felix Drexler

    Full Text Available Hepatitis C virus (HCV is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species; and sera from 2,939 bats (51 species. Three highly divergent rodent hepacivirus clades were detected in 27 (1.8% of 1,465 European bank voles (Myodes glareolus and 10 (1.9% of 518 South African four-striped mice (Rhabdomys pumilio. Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%. Our data enable new hypotheses regarding HCV evolution and encourage

  19. Molecular survey of rodent-borne Trypanosoma in Niger with special emphasis on T. lewisi imported by invasive black rats.

    Science.gov (United States)

    Dobigny, Gauthier; Poirier, Philippe; Hima, Karmadine; Cabaret, Odile; Gauthier, Philippe; Tatard, Caroline; Costa, Jean-Marc; Bretagne, Stéphane

    2011-03-01

    Invading rodent species can harbor parasites with potential transmission to native rodents and/or humans. To investigate trypanosomes prevalence in rodents, the spleen of 76 rodents from Niger identified by their karyotype was used as a DNA source for Trypanosoma detection using a newly developed qPCR assay. Of the invasive black rat, Rattus rattus, 71% (10/14) were PCR positive as well as 6% (4/62) of native African rodents. Sequences of ~400bp of the SSU rDNA gene identified phylogenetically close Trypanosoma lineages. Trypanosoma lewisi was present in all positive black rats and the sequences displayed 100% similarity with T. lewisi-infected humans in Senegal. T. lewisi was also detected in one Acomys johannis, suggesting a possible transmission to native species. In addition to improved knowledge of Trypanosoma diversity in rodents, our data underscore the introduction of the potentially pathogenic T. lewisi kinetoplastid through the human-mediated invasion of black rats all over West Africa.

  20. Rodent models for compulsive alcohol intake.

    Science.gov (United States)

    Hopf, F Woodward; Lesscher, Heidi M B

    2014-05-01

    Continued seeking and drinking of alcohol despite adverse legal, health, economic, and societal consequences is a central hallmark of human alcohol use disorders. This compulsive drive for alcohol, defined by resistance to adverse and deleterious consequences, represents a major challenge when attempting to treat alcoholism clinically. Thus, there has long been interest in developing pre-clinical rodent models for the compulsive drug use that characterizes drug addiction. Here, we review recent studies that have attempted to model compulsive aspects of alcohol and cocaine intake in rodents, and consider technical and conceptual issues that need to be addressed when trying to recapitulate compulsive aspects of human addiction. Aversion-resistant alcohol intake has been examined by pairing intake or seeking with the bitter tastant quinine or with footshock, and exciting recent work has used these models to identify neuroadaptations in the amygdala, cortex, and striatal regions that promote compulsive intake. Thus, rodent models do seem to reflect important aspects of compulsive drives that sustain human addiction, and will likely provide critical insights into the molecular and circuit underpinnings of aversion-resistant intake as well as novel therapeutic interventions for compulsive aspects of addiction.

  1. Spontaneous Type 2 Diabetic Rodent Models

    Science.gov (United States)

    Wang, Yang-wei; Sun, Guang-dong; Sun, Jing; Liu, Shu-jun; Wang, Ji; Xu, Xiao-hong; Miao, Li-ning

    2013-01-01

    Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes. PMID:23671868

  2. Carcinogenicity of azo colorants: influence of solubility and bioavailability.

    Science.gov (United States)

    Golka, Klaus; Kopps, Silke; Myslak, Zdislaw W

    2004-06-15

    In the past, azo colorants based on benzidine, 3,3'-dichlorobenzidine, 3,3'-dimethylbenzidine (o-tolidine), and 3,3'-dimethoxybenzidine (o-dianisidine) have been synthesized in large amounts and numbers. Studies in exposed workers have demonstrated that the azoreduction of benzidine-based dyes occurs in man. The metabolic conversion of benzidine-, 3,3'-dimethylbenzidine- and 3,3'-dimethoxybenzidine-based dyes to their (carcinogenic) amine precursors in vivo is a general phenomenon that must be considered for each member of this class of chemicals. Several epidemiological studies have demonstrated that the use of the benzidine-based dyes has caused bladder cancer in humans. However, in contrast to water-soluble dyes, the question of biological azoreduction of (practically insoluble) pigments has been a matter of discussion. As a majority of azo pigments are based on 3,3'-dichlorobenzidine, much of the available experimental data are focused on this group. Long-term animal carcinogenicity studies performed with pigments based on 3,3'-dichlorobenzidine did not show a carcinogenic effect. The absence of a genotoxic effect has been supported by mutagenicity studies with the 3,3'-dichlorobenzidine-based Pigment Yellow 12. Studies in which azo pigments based on 3,3'-dichlorobenzidine had been orally administered to rats, hamsters, rabbits and monkeys could generally not detect significant amounts of 3,3'-dichlorobenzidine in the urine. It, therefore, appears well established that the aromatic amine components from azo pigments based on 3,3'-dichlorobenzidine are practically not bioavailable. Hence, it is very unlikely that occupational exposure to insoluble azo pigments would be associated with a substantial risk of (bladder) cancer in man. According to current EU regulations, azo dyes based on benzidine, 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine have been classified as carcinogens of category 2 as "substances which should be regarded as if they are carcinogenic

  3. Polycyclic Aromatic Hydrocarbons In Edible Mushrooms from Niger Delta, Nigeria: Carcinogenic and Non-Carcinogenic Health Risk Assessment

    Science.gov (United States)

    Igbiri, Sorbari; Udowelle, Nnaemeka Arinze; Ekhator, Osazuwa Clinton; Asomugha, Rose Ngozi; Igweze, Zelinjo Nkeiruka; Orisakwe, Orish Ebere

    2017-02-01

    In the oil-rich Niger Delta, hydrocarbon pollution and oil spillages, gas flaring and sundry anthropogenic activities constitute sources of polycyclic aromatic hydrocarbons (PAHs), with food contamination playing a major role in human exposure. In this study we assessed PAH levels in wild and cultivated edible mushroom species consumed by the general population from the oil producing Niger Delta, Nigeria. The concentrations of USEPA-16 PAHs were determined by gas chromatography and carcinogenic and non-carcinogenic health risks were calculated. The concentrations of USEPA-16 PAHs ranged from 0.02 mg/kg – 3.37 mg/kg. The dietary intake of carcinogenic and non-carcinogenic USEPA-16 PAHs (Naphthalene, Acenaphthylene, Acenaphthene, Anthracene, Phenanthrene, Flourene, Flouranthene, Pyrene, Benzo[a]Anthracene, Chrysene, Benzo[a]Pyrene, Benzo[b]Flouranthene, Benzo[K]Flouranthene, Benzo[g,h,i] Perylene, Dibenz[a,h]Anthracene and Ideno[1,2,3-cd]Pyrene) for adults, adolescents and seniors ranged from 0.00 – 0.05 mg/kg/day, 0.00 – 0.06 mg/kg/day and 0.00 – 0.07 mg/kg/day. The BaPeq ranged from 0.02 – 2.76 with margin of exposure MOE values of BaP ranging from 3,500,000 to 700,000, 3,500,000 and 3,500,000 to 7,000,000 for adults, adolescents and seniors indicating very insignificant health risk. The incremental lifetime cancer risk was within the safe range of 1.56x10-8 – 1.73x10-6 with the highest calculated risk found for wild Pleurotus ostreatus mushroom species from the study area. Creative Commons Attribution License

  4. Development of an improved analytical method for the determination of carcinogenic polycyclic aromatic hydrocarbons in transformer oil.

    Science.gov (United States)

    Pillai, I; Ritchie, L; Heywood, R; Wilson, G; Pahlavanpour, B; Setford, S; Saini, S

    2005-02-04

    Polynuclear aromatic hydrocarbons (PAHs) are natural constituents of transformer oils and are essential in prolonging transformer in-service lifetime. Issues concerning PAH carcinogenicity demand methods that provide qualitative and quantitative information on the PAH composition of new and in-service oils to allow informed operational decisions to be made. However, current analytical methods focus on PAH fingerprinting, as opposed to quantitative analysis and are also cumbersome, relying on the use of large (>100 ml) volumes of organic solvents, some of which are hazardous. This paper reports a method for the improved quantification of carcinogenic PAHs in transformer oils that is both simple and repeatable. The method uses commercially available solid-phase extraction columns and millilitre volumes of relatively non-hazardous solvents. Extraction efficiencies of > or =74% were obtained for the Environmental Protection Agency priority PAHs. The method has potential for automation and high-throughput analysis and thus is of interest to industries that use transformer oils.

  5. Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets.

    Science.gov (United States)

    Rider, Cynthia V; Nyska, Abraham; Cora, Michelle C; Kissling, Grace E; Smith, Cynthia; Travlos, Gregory S; Hejtmancik, Milton R; Fomby, Laurene M; Colleton, Curtis A; Ryan, Michael J; Kooistra, Linda; Morrison, James P; Chan, Po C

    2014-07-01

    Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, 3-month and 2-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program's Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use.

  6. Carcinogenicity of individual and a mixture of dioxin-like compounds in female Harlan Sprague Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Walker, N.; Nyska, A. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Crockett, P. [Constella Group, Research Triangle Park, NC (US)] (and others)

    2004-09-15

    The human health risk posed by exposure to persistent organochlorine pollutants (POPs), including polychlorinated-dioxins (PCDDs), -furans (PCDFs) and - biphenyls (PCBs), present in the food and the environment is one of widespread concern throughout the industrialized world. The dioxin Toxic Equivalency Factor (TEF) approach is currently the most feasible interim approach for assessing and managing the risk posed by exposure to mixtures of these compounds and has been formally adopted by regulatory bodies in many countries, the International Programme on Chemical Safety and the World Health Organization. The TEF methodology is a relative potency scheme that estimates the total exposure and biological effects of a mixture of chemicals based on a common mechanism of action involving an initial binding of the compound to the Aryl hydrocarbon receptor (AhR). An implicit assumption of the TEF methodology is that the combined risk of effects of the different congeners is dose additive. Therefore, the total dioxin toxic equivalents (TEQs) of a mixture of PCDDs, PCDFs, and PCBs may be estimated by the summation of the mass of each compound in the mixture after adjustment for its potency relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While dose additivity is supported for certain mixtures for some biological endpoints in some experimental models, this has never been evaluated for cancer risk. Here we present a summary of four chronic rodent bioassay conducted by the National Toxicology Program (US Department of Health and Human Services) that evaluated the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3.3',4,4',5- pentachlorobiphenyl (PCB126) and 2,3,4,7,8 pentachlorodibenzofuran (PeCDF) and a mixture of these three dioxin-like compounds in female Harlan Sprague Dawley rats. Data from these studies will be used to test the hypothesis of dose-additivity of carcinogenicity by a defined mixture of dioxin-like compounds.

  7. 1,3-Propane sultone as an extremely potent human carcinogen: description of an exposed cohort in Germany.

    Science.gov (United States)

    Bolt, Hermann M; Golka, Klaus

    2012-01-01

    1,3-Propane sultone (1,3-PS) is a directly alkylating, genotoxic and carcinogenic substance. In rats, 1,3-PS induces local and systemic tumors at multiple sites, including the mammary gland, intestine, hematopoietic system, kidneys, and the central nervous system (CNS), especially in the form of gliomas. In one particular company, 1,3-PS had been manufactured in limited amounts in the 1950s and 1960s, and for a few purposes until the 1970s. The number of individuals having been in contact with the compound occupationally comprised 55 in total. Data were obtained from this group with an open question of legal compensation regarding an occupational disease. Particular emphasis was placed on malignancies occurring among the occupationally exposed persons. As cerebral gliomas are a major type of tumor induced by 1,3-PS experimentally, the occurrence of two glioblastomas among the previously exposed persons was significant. Three intestinal malignancies were recorded within the cases observed. It is also noteworthy that there was one case of a duodenal carcinoma, which is normally a rare human malignancy. Two hematopoietic/lymphatic malignancies were observed, and there was one case of a renal cell carcinoma. The types of malignancies within a group of only 55 exposed persons are surprisingly consistent with the results from rodent studies. Data clearly indicate that 1,3-PS is carcinogenic in humans. Evidence indicates that 12 cases with various neoplasms were legally compensated within the period of 1985-2010 as an occupational disease, based on the "opening clause" of § 9 (2) SGB VII of legislation in Germany.

  8. The carcinogenic air pollutant 3-nitrobenzanthrone induces GC to TA transversion mutations in human p53 sequences.

    Science.gov (United States)

    vom Brocke, Jochen; Krais, Annette; Whibley, Catherine; Hollstein, Monica C; Schmeiser, Heinz H

    2009-01-01

    3-Nitrobenzanthrone (3-NBA) is a potent mutagen and a suspected human carcinogen present in particulate matter of diesel exhaust and ambient air pollution. Employing an assay with human p53 knock-in (Hupki) murine embryonic fibroblasts (HUFs), we examined p53 mutations induced by 3-NBA and its active metabolite, N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA). Twenty-nine immortalized cultures (cell lines) from 89 HUF primary cultures exposed at passage 1 for 5 days to 2 microM 3-NBA harboured 22 different mutations in the human DNA-binding domain sequence of the Hupki p53 tumour suppressor gene. The most frequently observed mutation was GC to TA transversion (46%), corroborating previous mutation studies with 3-NBA, and consistent with the presence of persistent 3-NBA-guanosine adducts found in DNA of exposed rodents. Six of the transversions found solely in 3-NBA-treated HUFs have not been detected thus far in untreated HUFs, but have been found repeatedly in human lung tumours. (32)P-post-labelling adduct analysis of DNA from HUF cells treated with 2 microM 3-NBA for 5 days showed a pattern similar to that found in vivo, indicating the metabolic competence of HUF cells to metabolize 3-NBA to electrophilic intermediates. Total DNA binding was 160 +/- 56 per 10(7) normal nucleotides with N(2)-guanosine being the major adduct. In contrast, identical treatment with N-OH-3-ABA resulted in a 100-fold lower level of specific DNA adducts and no carcinogen-specific mutation pattern in the Hupki assay. This indicates that the level of DNA adduct formation by the mutagen is critical to obtain specific mutation spectra in the assay. Our results are consistent with previous experiments in Muta Mouse and are compatible with the possibility that diesel exhaust exposure contributes to mutation load in humans and to lung cancer risk.

  9. Studies of carcinogenicity of sodium chlorite in B6C3F1 mice.

    Science.gov (United States)

    Yokose, Y; Uchida, K; Nakae, D; Shiraiwa, K; Yamamoto, K; Konishi, Y

    1987-01-01

    The carcinogenic activities of sodium chlorite in B6C3F1 mice were examined. Sodium chlorite was given at concentrations of 0 (control), 0.025% (low dose), or 0.05% (high dose) in the drinking water of 150 female and 150 male mice for 80 weeks, after which time the animals were returned to distilled water without sodium chlorite. All mice were sacrificed 85 weeks from the beginning of the experiment. The incidence of tumor-bearing animals was 32% (control), 34% (low dose), and 26% (high dose) in female mice, and 46% (control), 57% (low dose), and 53% (high dose) in male mice. The types and incidence of neoplasms that occurred frequently in each group of both sexes were similar to those observed spontaneously in B6C3F1 mice. The incidence of lymphomas/leukemias in the high dose group of females (2%), however, was lower than that in the control group (15%). Furthermore, the incidence of pulmonary adenomas in the high dose group of males (12%) was higher than that in the control group (0%), but neither dose-related increases in the adenoma incidences nor increased incidences of the adenocarcinomas were observed. These results indicated no clear evidence of a carcinogenic potential of sodium chlorite in B6C3F1 mice. PMID:3447900

  10. Anti-proliferative activities of sinigrin on carcinogen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Jie, Meng; Cheung, Wan Man; Yu, Vivian; Zhou, Yanling; Tong, Pak Ho; Ho, John W S

    2014-01-01

    Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer.

  11. Evaluation of the Xpa-Deficient Transgenic Mouse Model for Short-Term Carcinogenicity Testing: 9-Month Studies with Haloperidol, Reserpine, Phenacetin, and D-Mannitol

    NARCIS (Netherlands)

    Lina, B.A.R.; Woutersen, R.A.; Bruijntjes, J.P.; Benthem, J. van; Berg, J.A.H. van den; Monbaliu, J.; Thoolen, B.J.J.M.; Beems, R.B.; Kreijl, C.F. van

    2004-01-01

    As part of the international evaluation program coordinated by ILSI/HESI, the potential of DNA repair deficient Xpa-/- mice and the double knockout Xpa-/-.p53+/- mice for short term carcinogenicity assays was evaluated. For comparison also wild-type C57BL/6 mice (WT) were included in these studies.

  12. Assessment of Carcinogenicity of di(2-ethylhexyl) phthalate in a short-term assay using Xpa(-/-) and Xpa(-/-)/p53(+/-) mice

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Bertram, Margareta; Aarup, V.;

    2002-01-01

    The potential of Xpa(-/-) and Xpa(-/-)/p53(+/-) mice for short-term carcinogenicity assays was evaluated with di(2-ethylhexyl)phthalate (DEHP). Groups of 15 male and female Xpa(-/-) mice, received diets containing 0, 1,500, 3, 000, or 6,000 ppm DEHP, and wild-type (WT) and Xpa(-/-)/p53(+/-) mice 0...

  13. Effect of an invasive plant and moonlight on rodent foraging behavior in a coastal dune ecosystem.

    Science.gov (United States)

    Johnson, Matthew D; De León, Yesenia L

    2015-01-01

    Understanding how invasive plants may alter predator avoidance behaviors is important for granivorous rodents because their foraging can trigger ripple effects in trophic webs. Previous research has shown that European beach grass Ammophila arenaria, an invasive species in coastal California, affects the predation of other seeds by the rodents Microtus californicus, Peromyscus maniculatus, and Reithrodontomys megalotis. This may be due to lower perceived predation risk by rodents foraging in close proximity to the cover provided by Ammophila, but this mechanism has not yet been tested. We examined the perceived predation risk of rodents by measuring the 'giving up density' of food left behind in experimental patches of food in areas with and without abundant cover from Ammophila and under varying amount of moonlight. We found strong evidence that giving up density was lower in the thick uniform vegetation on Ammophila-dominated habitat than it was in the more sparsely and diversely vegetated restored habitat. There was also evidence that moonlight affected giving up density and that it mediated the effects of habitat, although with our design we were unable to distinguish the effects of lunar illumination and moon phase. Our findings illustrate that foraging rodents, well known to be risk-averse during moonlit nights, are also affected by the presence of an invasive plant. This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. Future research in this system should work to unravel the complex trophic links formed by a non-native invasive plant (i.e., Ammophila) providing cover favored by native rodents, which likely forage on and potentially limit the recruitment of native and non-native plants, some of which have ecosystem consequences of their own.

  14. Effect of an invasive plant and moonlight on rodent foraging behavior in a coastal dune ecosystem.

    Directory of Open Access Journals (Sweden)

    Matthew D Johnson

    Full Text Available Understanding how invasive plants may alter predator avoidance behaviors is important for granivorous rodents because their foraging can trigger ripple effects in trophic webs. Previous research has shown that European beach grass Ammophila arenaria, an invasive species in coastal California, affects the predation of other seeds by the rodents Microtus californicus, Peromyscus maniculatus, and Reithrodontomys megalotis. This may be due to lower perceived predation risk by rodents foraging in close proximity to the cover provided by Ammophila, but this mechanism has not yet been tested. We examined the perceived predation risk of rodents by measuring the 'giving up density' of food left behind in experimental patches of food in areas with and without abundant cover from Ammophila and under varying amount of moonlight. We found strong evidence that giving up density was lower in the thick uniform vegetation on Ammophila-dominated habitat than it was in the more sparsely and diversely vegetated restored habitat. There was also evidence that moonlight affected giving up density and that it mediated the effects of habitat, although with our design we were unable to distinguish the effects of lunar illumination and moon phase. Our findings illustrate that foraging rodents, well known to be risk-averse during moonlit nights, are also affected by the presence of an invasive plant. This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. Future research in this system should work to unravel the complex trophic links formed by a non-native invasive plant (i.e., Ammophila providing cover favored by native rodents, which likely forage on and potentially limit the recruitment of native and non-native plants, some of which have ecosystem consequences of their own.

  15. The Prevalence of Trypanosoma cruzi, the Causal Agent of Chagas Disease, in Texas Rodent Populations.

    Science.gov (United States)

    Aleman, Adriana; Guerra, Trina; Maikis, Troy J; Milholland, Matthew T; Castro-Arellano, Ivan; Forstner, Michael R J; Hahn, Dittmar

    2017-03-01

    Rodent species were assessed as potential hosts of Trypanosoma cruzi, the etiologic agent of Chagas disease, from five sites throughout Texas in sylvan and disturbed habitats. A total of 592 rodents were captured, resulting in a wide taxonomic representation of 11 genera and 15 species. Heart samples of 543 individuals were successfully analyzed by SybrGreen-based quantitative PCR (qPCR) targeting a 166 bp fragment of satellite DNA of T. cruzi. Eight rodents representing six species from six genera and two families were infected with T. cruzi. This is the first report of T. cruzi in the pygmy mouse (Baiomys taylori) and the white-footed mouse (Peromyscus leucopus) for the USA. All infected rodents were from the southernmost site (Las Palomas Wildlife Management Area). No differences in pathogen prevalence existed between disturbed habitats (5 of 131 tested; 3.8%) and sylvan habitats (3 of 40 tested; 7.5%). Most positives (n = 6, 16% prevalence) were detected in late winter with single positives in both spring (3% prevalence) and fall (1% prevalence). Additionally, 30 Triatoma insects were collected opportunistically from sites in central Texas. Fifty percent of these insects, i.e., 13 T. gerstaeckeri (68%), and two T. lecticularia (100%) were positive for T. cruzi. Comparative sequence analyses of 18S rRNA of samples provided identical results with respect to detection of the presence or absence of T. cruzi and assigned T. cruzi from rodents collected in late winter to lineage TcI. T. cruzi from Triatoma sp. and rodents from subsequent collections in spring and fall were different, however, and could not be assigned to other lineages with certainty.

  16. Environmental enrichment of laboratory rodents: the answer depends on the question.

    Science.gov (United States)

    Toth, Linda A; Kregel, Kevin; Leon, Lisa; Musch, Timothy I

    2011-08-01

    Efforts to refine the care and use of animals in research have been ongoing for many years and have led to general standardization of rodent models, particularly with regard to animal housing, genetics, and health status. Concurrently, numerous informal practices and recommendations have been promulgated with the laudable intent of promoting general animal wellbeing through so-called enrichment of the cage environment. However, the variety of housing conditions fostered by efforts at environmental enrichment (EE) complicates the goal of establishing standardized or even defined environments for laboratory rodents. Many studies over the years have sought to determine whether or how various enrichment strategies affect the behavior and physiology of laboratory rodents. The findings, conclusions, and interpretations of these studies are mixed, particularly with regard to their application across rodent species, strains, genders, and ages; whether or how they affect the animals and the science; and, in some cases, whether the effects are positive, negative, or neutral in terms of animal wellbeing. Crucial issues related to the application of EE in research settings include its poorly defined effect on the animals, the potential for increased variability in the data, poor definition across labs and in publications, and potential for animal or scientific harm. The complexities, uncertainties, interpretational conundrums, varying conclusions, and lack of consensus in the EE literature warrant careful assessment of the benefits and liabilities associated with implementing such interventions. Reliance on evidence, professional judgment, and performance standards are crucial in the development of EE strategies.

  17. Helminthes of synanthropic rodents (Rodentia: Muridae) from Dakahlia and Menoufia, Egypt.

    Science.gov (United States)

    Elshazly, Atef M; Awad, Soha I; Azab, Manar S; Elsheikha, Hany M; Abdel-Gawad, Abdel Gawad E; Khalil, Hazem H M; Morsy, Tosson A

    2008-12-01

    A cross-sectional survey was conducted to monitor and compare the prevalence of helminthes in rodents from Dakahlia and Menoufia governorates. The domestic rodents (271) were Rattus norvegicus, Rattus rattus frugivorous, Rattus r. alexandrinus, & Mus musculus. The overall prevalence of helminthes was 52.8%. In Dakahlia, 72/145 rats (49.6%) were infected. The highest prevalence of infection was in R. r. frugivorous 43 (60.4%), then R. r. alexandrinus 44 (47.7%), R. norvegicus 38 (44.7%), and the lowest was M. musculus 20 (40%). In Menoufia, 71/126 rats (56.3%) were infected. The highest prevalence of infection was in R. r. frugivorous 36 (77.7%), then M. musculus 27 (48.1%), R. norvegicus 23 (47.8%), and the lowest was in R. r. alexandrinus 40 (47.5%). A total of 24 species of helminthes (11 trematodes, 4 cestodes & 10 nematodes) were identified among the 271 rodents. The commonest trematode was Mesostephanus aegypticus followed by Stictodora tridactyla. The commonest cestode was Hymenolepis diminuta followed by Taenia taeniaformis. The commonest nematode was Capillaria hepatica followed by Trichurus muris. Given the zoonotic potential of rodents' parasites and since several residential, commercial, and agricultural sites exist in the examined geographic areas, the potential health risk should not be ignored.

  18. Seed preferences by rodents in the agri?environment and implications for biological weed control

    OpenAIRE

    Fischer, Christina;Türke, Manfred

    2016-01-01

    Summary Post?dispersal seed predation and endozoochorous seed dispersal are two antagonistic processes in relation to plant recruitment, but rely on similar preconditions such as feeding behavior of seed consumers and seed traits. In agricultural landscapes, rodents are considered important seed predators, thereby potentially providing regulating ecosystem services in terms of biological weed control. However, their potential to disperse seeds endozoochorously is largely unknown. We exposed s...

  19. Rodents and risk in the Mekong Delta of Vietnam: seroprevalence of selected zoonotic viruses in rodents and humans.

    Science.gov (United States)

    Van Cuong, Nguyen; Carrique-Mas, Juan; Vo Be, Hien; An, Nguyen Ngoc; Tue, Ngo Tri; Anh, Nguyet Lam; Anh, Pham Hong; Phuc, Nguyen The; Baker, Stephen; Voutilainen, Liina; Jääskeläinen, Anne; Huhtamo, Eili; Utriainen, Mira; Sironen, Tarja; Vaheri, Antti; Henttonen, Heikki; Vapalahti, Olli; Chaval, Yannick; Morand, Serge; Bryant, Juliet E

    2015-01-01

    In the Mekong Delta in southern Vietnam, rats are commonly traded in wet markets and sold live for food consumption. We investigated seroprevalence to selected groups of rodent-borne viruses among human populations with high levels of animal exposure and among co-located rodent populations. The indirect fluorescence antibody test (IFAT) was used to determine seropositivity to representative reference strains of hantaviruses (Dobrava virus [DOBV], Seoul virus [SEOV]), cowpox virus, arenaviruses (lymphocytic choriomeningitis virus [LCMV]), flaviviruses (tick-borne encephalitis virus [TBEV]), and rodent parechoviruses (Ljungan virus), using sera from 245 humans living in Dong Thap Province and 275 rodents representing the five common rodent species sold in wet markets and present in peridomestic and farm settings. Combined seropositivity to DOBV and SEOV among the rodents and humans was 6.9% (19/275) and 3.7% (9/245), respectively; 1.1% (3/275) and 4.5% (11/245) to cowpox virus; 5.4% (15/275) and 47.3% (116/245) for TBEV; and exposure to Ljungan virus was 18.8% (46/245) in humans, but 0% in rodents. Very little seroreactivity was observed to LCMV in either rodents (1/275, 0.4%) or humans (2/245, 0.8%). Molecular screening of rodent liver tissues using consensus primers for flaviviruses did not yield any amplicons, whereas molecular screening of rodent lung tissues for hantavirus yielded one hantavirus sequence (SEOV). In summary, these results indicate low to moderate levels of endemic hantavirus circulation, possible circulation of a flavivirus in rodent reservoirs, and the first available data on human exposures to parechoviruses in Vietnam. Although the current evidence suggests only limited exposure of humans to known rodent-borne diseases, further research is warranted to assess public health implications of the rodent trade.

  20. Serological Prevalence Against Japanese Encephalitis Virus-Serocomplex Flaviviruses in Commensal and Field Rodents in South China.

    Science.gov (United States)

    Chen, Shao-Wei; Jiang, Li-Na; Zhong, Xue-Shan; Zheng, Xue-Yan; Ma, Shu-Juan; Xiong, Yi-Quan; Zhou, Jun-Hua; Li, Xing; Ke, Xue-Mei; Zhou, Wen; Chen, Qing

    2016-12-01

    Japanese encephalitis caused by Japanese encephalitis virus (JEV) is an endemic zoonotic disease of high public health importance in the Asian Pacific region. The aim of this study was to investigate the presence of JEV infection in commensal and field rodents in South China. RNA copies of JEV were detected in brain samples of rodents using real-time RT-PCR. Detection of serum against JEV-reactive antibodies was performed using indirect enzyme-linked immunosorbent assay and microneutralization test. In total, 198 rodents were collected from Guangzhou City and Xiamen City between November 2013 and May 2014. JEV RNA was not detected in 188 brain samples. Forty-four in 96 serum samples (45.8%) were positive for JEV-reactive IgG antibodies. The prevalence of neutralizing antibodies to against JEV-reactive in these serum samples was 61.5% (24/39), with titers ranging from 1:10 to 1:56. Rodents are not known to play a role in transmission of JEV in Asia, nor is there an evidence to support a role for rodents in transmission of other related flaviviruses in China. However, in the current study, we detected evidence of JEV-reactive antibodies in large numbers of Rattus norvegicus and Rattus losea Swinhoe. Further studies of rodents as potential hosts of JEV or other related flaviviruses are warranted.

  1. Prevalence of leptospirosis and toxoplasmosis: a study of rodents and shrews in cultivated and fallow land, Morogoro rural district, Tanzania.

    Science.gov (United States)

    Mgode, Georgies F; Katakweba, Abdul S; Mhamphi, Ginethon G; Fwalo, Frank; Bahari, Mohamed; Mdangi, Mashaka; Kilonzo, Bukheti S; Mulungu, Loth S

    2014-07-01

    Leptospirosis and toxoplasmosis are among understudied zoonotic diseases that are also not diagnosed routinely in Tanzania. Humans get leptospirosis and toxoplasmosis through contact with an environment contaminated with Leptospira bacteria and Toxoplasma protozoa from reservoir hosts, which are rodents and cats, respectively. The objective of this study was to determine the prevalence of Leptospira and Toxoplasma infections in rodents and shrews in Mikese area of Morogoro Rural District in eastern Tanzania. A total of 89 rodents and one shrew from cultivated and fallow land were tested for leptospirosis using six Leptospira serovars: Sokoine, Kenya, Canicola, Lora, Hebdomadis and Pomona. Toxoplasmosis was determined in 46 rodents brain smears. The prevalence of leptospirosis was 25.8%, and Leptospira serovar Sokoine was the most prevalent serovar (16.9%). Toxoplasma was detected in one rodent (2.17%) individual while three rodent individuals had Toxoplasma-like parasites hence were considered suspect positive. Findings suggest potential existence of human leptospirosis which needs to be further investigated. Public awareness of leptospirosis and toxoplasmosis should be promoted and their diagnosis considered in patients in health care facilities.

  2. A fundamental oscillatory state of isolated rodent hippocampus.

    Science.gov (United States)

    Wu, Chiping; Shen, Hui; Luk, Wah Ping; Zhang, Liang

    2002-04-15

    Population neuronal rhythms of various frequencies are observed in the rodent hippocampus during distinct behavioural states. However, the question of whether the hippocampus exhibits properties of spontaneous rhythms and population synchrony in isolation has not been definitively answered. To address this, we developed a novel preparation for studying neuronal rhythms in a relatively large hippocampal tissue in vitro. We isolated the whole hippocampus from mice up to 28 days postnatal age, removing the dentate gyrus while preserving the functional CA3-to-CA1 connections. Placing the hippocampal isolate in a perfusion chamber for electrophysiological assessment extracellular recordings from the CA1 revealed rhythmic field potential of 0.5 to interneurons. Similar spontaneous field rhythms were also observed in the hippocampal isolate prepared from young gerbils and rats. Based on these data, we postulate that the spontaneous rhythms represent a fundamental oscillatory state of the hippocampal circuitry isolated from extra-hippocampal inputs.

  3. Bartonella infection in rodents and their flea ectoparasites: an overview.

    Science.gov (United States)

    Gutiérrez, Ricardo; Krasnov, Boris; Morick, Danny; Gottlieb, Yuval; Khokhlova, Irina S; Harrus, Shimon

    2015-01-01

    Epidemiological studies worldwide have reported a high prevalence and a great diversity of Bartonella species, both in rodents and their flea parasites. The interaction among Bartonella, wild rodents, and fleas reflects a high degree of adaptation among these organisms. Vertical and horizontal efficient Bartonella transmission pathways within flea communities and from fleas to rodents have been documented in competence studies, suggesting that fleas are key players in the transmission of Bartonella to rodents. Exploration of the ecological traits of rodents and their fleas may shed light on the mechanisms used by bartonellae to become established in these organisms. The present review explores the interrelations within the Bartonella-rodent-flea system. The role of the latter two components is emphasized.

  4. Susceptibility of laboratory rodents to Trichinella papuae.

    Science.gov (United States)

    Sadaow, Lakkhana; Intapan, Pewpan M; Boonmars, Thidarut; Morakote, Nimit; Maleewong, Wanchai

    2013-12-01

    Members of the genus Trichinella are small nematodes that can infect a wide range of animal hosts. However, their infectivity varies depending on the parasite and host species combination. In this study, we examined the susceptibility of 4 species of laboratory rodents, i.e., mice, rats, hamsters, and gerbils to Trichinella papuae, an emerging non-encapsulated Trichinella species. Trichinella spiralis and Trichinella pseudospiralis were also included in this study for comparison. Fifteen animals of each rodent species were infected orally with 100 muscle larvae of each Trichinella species. Intestinal worm burden was determined at day 6 and 10 post-inoculation (PI). The numbers of muscle larvae were examined at day 45 PI. The reproductive capacity index (RCI) of the 3 Trichinella species in different rodent hosts was determined. By day 6 PI, 33.2-69.6% of the inoculated larvae of the 3 Trichinella species became adult worms in the small intestines of the host animals. However, in rats, more than 96% of adult worms of all 3 Trichinella species were expelled from the gut by day 10 PI. In gerbils, only 4.8-18.1% of adult worms were expelled by day 10 PI. In accordance with the intestinal worm burden and the persistence of adults, the RCI was the highest in gerbils with values of 241.5±41.0 for T. papuae, 432.6±48 for T. pseudospiralis, and 528.6±20.6 for T. spiralis. Hamsters ranked second and mice ranked third in susceptibility in terms of the RCI, Rats yielded the lowest parasite RCI for all 3 Trichinella species. Gerbils may be an alternative laboratory animal for isolation and maintenance of Trichinella spp.

  5. Building an organ-specific carcinogenic database for SAR analyses.

    Science.gov (United States)

    Young, John; Tong, Weida; Fang, Hong; Xie, Qian; Pearce, Bruce; Hashemi, Ray; Beger, Richard; Cheeseman, Mitchell; Chen, James; Chang, Yuan-Chin; Kodell, Ralph

    2004-09-10

    FDA reviewers need a means to rapidly predict organ-specific carcinogenicity to aid in evaluating new chemicals submitted for approval. This research addressed the building of a database to use in developing a predictive model for such an application based on structure-activity relationships (SAR). The Internet availability of the Carcinogenic Potency Database (CPDB) provided a solid foundation on which to base such a model. The addition of molecular structures to the CPDB provided the extra ingredient necessary for SAR analyses. However, the CPDB had to be compressed from a multirecord to a single record per chemical database; multiple records representing each gender, species, route of administration, and organ-specific toxicity had to be summarized into a single record for each study. Multiple studies on a single chemical had to be further reduced based on a hierarchical scheme. Structural cleanup involved removal of all chemicals that would impede the accurate generation of SAR type descriptors from commercial software programs; that is, inorganic chemicals, mixtures, and organometallics were removed. Counterions such as Na, K, sulfates, hydrates, and salts were also removed for structural consistency. Structural modification sometimes resulted in duplicate records that also had to be reduced to a single record based on the hierarchical scheme. The modified database containing 999 chemicals was evaluated for liver-specific carcinogenicity using a variety of analysis techniques. These preliminary analyses all yielded approximately the same results with an overall predictability of about 63%, which was comprised of a sensitivity of about 30% and a specificity of about 77%. Copyright Taylor & Francis Inc.

  6. Clinical aspects of rodent dental anatomy.

    Science.gov (United States)

    Crossley, D A

    1995-12-01

    The order Rodentia is vast, encompassing a large number of species with significant anatomical variations developed during natural adaptation to differing habitats. Many veterinarians have little knowledge of the anatomy of species other than the commoner domestic large herbivores and small carnivores. Clinicians require a basic knowledge of the relevant anatomy of species they are likely to be asked to treat. This article provides sufficient working knowledge of the oral and dental anatomy of those rodents commonly kept as pets to enable veterinarians to interpret clinical and radiographic findings when investigating suspected dental disease.

  7. Convergent and Divergent Adaptations of Subterranean Rodents

    DEFF Research Database (Denmark)

    Fang, Xiaodong

    ) have evolved convergent and divergent traits in many of their morphological, physiological, and/or behavioral characteristics, which facilitate their adaptions to a similar underground burrowing life style. For example, all these three rodents show degenerate visual acuity and advanced sensory systems...... in the dark; they display remarkable tolerance to a living environment with an excess of carbon dioxide and ammonia, but lack of oxygen; they exhibit extraordinarily long lives, and keep a fantastic resistance to cancer and other aging-associated diseases. In this study, we reported the genomic...

  8. [Advances in non-carcinogenic toxicity of trichloroethylene].

    Science.gov (United States)

    Huang, Peiwu; Li, Xuan; Liu, Wei; Liu, Jianjun

    2015-09-01

    Trichloroethylene (TCE) is a widely used organic solvent and an important industrial material. Due to mass production and use, and improper waste disposal, TCE has become a common environmental contaminant, so there is a wide range of occupationally and environmentally exposed population. Occupational and environmental exposure to TCE can produce toxic effects on multiple organs and systems. This paper is a review of the immunotoxicity, reproductive toxicity, neurotoxicity, teratogenic effect and other non-carcinogenic toxic effects of TCE from the aspects of epidemiological study, experimental evidence on animals and toxic mechanisms.

  9. Novel Uses of In Vitro Data to Develop Quantitative Biological Activity Relationship Models for in Vivo Carcinogenicity Prediction.

    Science.gov (United States)

    Pradeep, Prachi; Povinelli, Richard J; Merrill, Stephen J; Bozdag, Serdar; Sem, Daniel S

    2015-04-01

    The availability of large in vitro datasets enables better insight into the mode of action of chemicals and better identification of potential mechanism(s) of toxicity. Several studies have shown that not all in vitro assays can contribute as equal predictors of in vivo carcinogenicity for development of hybrid Quantitative Structure Activity Relationship (QSAR) models. We propose two novel approaches for the use of mechanistically relevant in vitro assay data in the identification of relevant biological descriptors and development of Quantitative Biological Activity Relationship (QBAR) models for carcinogenicity prediction. We demonstrate that in vitro assay data can be used to develop QBAR models for in vivo carcinogenicity prediction via two case studies corroborated with firm scientific rationale. The case studies demonstrate the similarities between QBAR and QSAR modeling in: (i) the selection of relevant descriptors to be used in the machine learning algorithm, and (ii) the development of a computational model that maps chemical or biological descriptors to a toxic endpoint. The results of both the case studies show: (i) improved accuracy and sensitivity which is especially desirable under regulatory requirements, and (ii) overall adherence with the OECD/REACH guidelines. Such mechanism based models can be used along with QSAR models for prediction of mechanistically complex toxic endpoints. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Exposure and Metabolic Activation Biomarkers of Carcinogenic Tobacco-Specific Nitrosamines.

    Science.gov (United States)

    Hecht, Stephen S; Stepanov, Irina; Carmella, Steven G

    2016-01-19

    , blood, and toenails. Urinary and serum NNAL have been related to lung cancer risk, and urinary NNN has been related to esophageal cancer risk in prospective epidemiology studies. These results are consistent with carcinogenicity studies of NNK, NNAL, and NNN in rats, which show that NNK and NNAL induce mainly lung tumors, while NNN causes tumors of the esophagus and oral cavity. Biomarkers of metabolic activation of NNK and NNN applied in human studies include the metabolism of deuterium labeled substrates to distinguish NNK and NNN metabolism from that of nicotine and the determination of DNA and hemoglobin adducts in tissues, blood, and oral cells from people exposed to tobacco products. As these methods are continually improved in parallel with the ever increasing sensitivity and selectivity of mass spectrometers, development of a comprehensive biomarker panel for identifying tobacco users at high risk for cancer appears to be a realistic goal. Targeting high risk individuals for smoking cessation and cancer surveillance can potentially decrease the risk of developing fatal cancers.

  11. Ecomorphological analysis of the astragalo-calcaneal complex in rodents and inferences of locomotor behaviours in extinct rodent species

    OpenAIRE

    Ginot, Samuel; Hautier, Lionel; Marivaux, Laurent; Vianey-Liaud, Monique

    2016-01-01

    Studies linking postcranial morphology with locomotion in mammals are common. However, such studies are mostly restricted to caviomorphs in rodents. We present here data from various families, belonging to the three main groups of rodents (Sciuroidea, Myodonta, and Ctenohystrica). The aim of this study is to define morphological indicators for the astragalus and calcaneus, which allow for inferences to be made about the locomotor behaviours in rodents. Several specimens were dissected and des...

  12. KEYNOTE LECTURES-KL1 New development in risk assessment of genotoxic carcinogens in foods

    Institute of Scientific and Technical Information of China (English)

    CHEN Jun-Shi

    2006-01-01

    @@ The no-observed-effect level (NOEL) in a study of carcinogenicity for compounds that are both genotoxic and carcinogenic represents the limit of detection in that bioassay, rather than an estimate of a possible threshold. Therefore, for those genotoxic and carcinogenic contaminants (e.g. acrylamides, PAHs, etc.) in foods it is not possible to develop health-based guidance values (e.g. ADI or PTWI) using the traditional NOEL and safety/uncertainty factors.

  13. Comment on the significance of positive carcinogenicity studies using gavage as the route of exposure.

    OpenAIRE

    Perera, F.; Brennan, T. (Thomas); Fouts, J. R.

    1989-01-01

    There is continuing controversy, extending into regulatory matters, over the significance to human health of positive results in carcinogenicity studies in animals using the gavage technique as the route of exposure. Our review of a nonrandom sample of 117 chemicals or chemical processes listed as known or reasonably anticipated to be carcinogenic in the National Toxicology Program's Third Annual Report on Carcinogens provides support for the validity of the gavage route in such studies. Twen...

  14. DNA adducts in human tissues:biomarkers of exposure to carcinogens in tobacco smoke

    OpenAIRE

    Phillips, D.H.

    1996-01-01

    Tobacco smoking causes millions of cancer deaths annually. Tobacco smoke is a complex mixture of thousands of chemicals including many known animal carcinogens. Because many carcinogens from DNA adducts in target animal or human tissues, the detection of the formation of adducts using such methods as postlabeling, immunoassay, fluorescence spectroscopy, and mass spectrometry is a means of monitoring human exposure to tobacco carcinogens. Smokers are at increased risk of cancer in many organs,...

  15. It is time to regulate carcinogenic tobacco-specific nitrosamines in cigarette tobacco

    OpenAIRE

    Hecht, Stephen S.

    2014-01-01

    The Family Smoking Prevention and Tobacco Control Act gives the Food and Drug Administration power to regulate tobacco products. This commentary calls for immediate regulation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN) in cigarette tobacco as a logical path to cancer prevention. NNK and NNN, powerful carcinogens in laboratory animals, have been evaluated as “carcinogenic to humans” by the International...

  16. [The evaluation of carcinogenic effect in rats and mice after intraperitoneal administration of refractory ceramic fibers].

    Science.gov (United States)

    Krajnow, A; Lao, I; Stetkiewicz, J; Wiecek, E

    1998-01-01

    The carcinogenic effect of Langfaser and Thermowool ceramic fibres was assessed in Wistar rats and BALB/C mice. Fibres were administered into the animal peritoneal cavity in doses of 25 and 5 mg, and the animals were left for survival. Langfaser and Thermowool ceramic fibres were found carcinogenic. The carcinogenic properties of Thermowool ceramic fibre can be compared to those of Krokidoit UICC asbestos.

  17. Smaller but not Secondary: Evidence of Rodents in Archaeological Context in India

    Directory of Open Access Journals (Sweden)

    Vijay Sathe

    2017-06-01

    Full Text Available The small site archaeology has a remarkable potential to contribute on many greater issues in archaeological studies. Similarly, micro dimensional data of any category should prove to be of great importance if studied judiciously. The present paper intends to point out this very fact with a special reference to skeletal remains of micromammals in the category of rodents as a special case. This topic has been specifically undertaken because it is largely observed that such skeletal material tends to be overlooked and sometimes even totally discarded as of no archaeological significance. Rats and mice (muroids, Order: Rodentia are one of the world’s ubiquitous small rodents whose antiquity in India goes back to the Tertiary period. Its skeletal remains have been reported from several archaeological sites in India with temporal range of about 20 ka. Rodents have the potential to provide palaeoenvironmental information not attainable from other animal groups. The fact is well appreciated in palaeoentology but unfortunately remains to be confronted in archaeological context so far. The present paper ventures to ponder upon the possibilities of palaeoenvironmental interpretations of rodent fauna in archaeological record. A sizable assemblage of microvertebrates excavated from an Early Historic site of Kopia, Dist. Sant Kabirnagar (Uttar Pradesh state of India offers a case study of microfaunal interpretations. Evidence of muroid’s contribution to the diet of ancient human population is discussed with reference to several existing hunting gathering communities practicing small game and the 'Musehars', aborigines living in the interiors of Gangetic plains. It provides a ready database for the dietary inferences with regard to the rodent fauna that are interpreted from archaeological perspective. The paper demonstrates multifold implications of evidence of rats and mice in archaeololgical record that have significant bearing on the ecology

  18. Rodent-Mediated Interactions Among Seed Species of Differing Quality in a Shrubsteppe Ecosystem

    Science.gov (United States)

    Beard, Karen H.; Faulhaber, Craig A.; Howe, Frank P.; Edwards, Thomas C.

    2013-01-01

    Interactions among seeds, mediated by granivorous rodents, are likely to play a strong role in shrubsteppe ecosystem restoration. Past studies typically consider only pairwise interactions between preferred and less preferred seed species, whereas rangeland seedings are likely to contain more than 2 seed species, potentially leading to complex interactions. We examined how the relative proportion of seeds in a 3-species polyculture changes rodent seed selectivity (i.e., removal) and indirect interactions among seeds. We presented 2 rodent species, Peromyscus maniculatus (deer mice) and Perognathus parvus (pocket mice), in arenas with 3-species seed mixtures that varied in the proportion of a highly preferred, moderately preferred, and least preferred seed species, based on preferences determined in this study. We then conducted a field experiment in a pocket mouse—dominated ecosystem with the same 3-species seed mixtures in both “treated” (reduced shrub and increased forb cover) and “untreated” shrubsteppe. In the arena experiment, we found that rodents removed more of the highly preferred seed when the proportions of all 3 seeds were equal. Moderately preferred seeds experienced increased removal when the least preferred seed was in highest proportion. Removal of the least preferred seed increased when the highly preferred seed was in highest proportion. In the field experiment, results were similar to those from the arena experiment and did not differ between treated and untreated shrubsteppe areas. Though our results suggest that 3-species mixtures induce complex interactions among seeds, managers applying these results to restoration efforts should carefully consider the rodent community present and the potential fate of removed seeds.

  19. Effects of glyphosate exposure on sperm concentration in rodents: A systematic review and meta-analysis.

    Science.gov (United States)

    Cai, Wenyan; Ji, Ying; Song, Xianping; Guo, Haoran; Han, Lei; Zhang, Feng; Liu, Xin; Zhang, Hengdong; Zhu, Baoli; Xu, Ming

    2017-07-29

    Correlation between exposure to glyphosate and sperm concentrations is important in reproductive toxicity risk assessment for male reproductive functions. Many studies have focused on reproductive toxicity on glyphosate, however, results are still controversial. We conducted a systematic review of epidemiological studies on the association between glyphosate exposure and sperm concentrations of rodents. The aim of this study is to explore the potential adverse effects of glyphosate on reproductive function of male rodents. Systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Embase, WANFANG and CNKI databases with different combinations of glyphosate exposure and sperm concentration. 8 studies were eventually identified and random-effect model was conducted. Heterogeneity among study results was calculated via chi-square tests. Ten independent experimental datasets from these eight studies were acquired to synthesize the random-effect model. A decrease in sperm concentrations was found with mean difference of sperm concentrations(MDsperm)=-2.774×10(6)/sperm/g/testis(95%CI=-0.969 to -4.579) in random-effect model after glyphosate exposure. There was also a significant decrease after fitting the random-effect model: MDsperm=-1.632×10(6)/sperm/g/testis (95%CI=-0.662 to -2.601). The results of meta-analysis support the hypothesis that glyphosate exposure decreased sperm concentration in rodents. Therefore, we conclude that glyphosate is toxic to male rodent's reproductive system. Copyright © 2017. Published by Elsevier B.V.

  20. Biological characterisation of Cryptosporidium parvum isolates of wildlife rodents in Poland.

    Science.gov (United States)

    Bednarska, Malgorzata; Bajer, Anna; Kulis, Karolina; Sinski, Edward

    2003-01-01

    The study was undertaken to characterise the C. parvum isolates originating from naturally infected woodland and field rodents: Clethrionomys glareolus (CG), Apodemus flavicollis (AF) and Microtus arvalis (MA). We found that the measurements of oocyst dimensions and oocyst morphology did not allow distinction between the parasite isolates from the 3 rodent species. The mean dimensions were: for CG 4.67 x 4.21, for AF 4.65 x 4.14 and for MA 4.66 x 4.16. These 3 groups of isolates have produced significantly different pictures of infection in C57BL/6 mice. The overall mean oocysts output was: in CG-mice 41,739, in AF-mice 18,000, in MA-mice 10,384 oocysts/1 g of faeces. From these data we suggest that rodent isolates of C. parvum could represent new subgroups in so-called "mouse" C. parvum strain. The successful cross-transmission from wild hosts to laboratory rodents and the close similarity of COWP sequence between our isolates and "mouse" genotype and between "mouse" and zoonotic genotype of C. parvum (genotype C) inform us that all these isolates should be treated as potentially hazardous for human health.

  1. The Carcinogenic Agent Azoxymethane (AOM) Enhances Early Inflammation-induced Colon Crypt Pathology

    DEFF Research Database (Denmark)

    Venning, Freja Albjerg; Claesson, Mogens Helweg; Kissow, Hannelouise

    2013-01-01

    mice and SCID mice with transfer colitis. AOM by itself did result in neither weight loss nor inflammation although treatment affected crypt widths and numbers. Although AOM together with T cell transfer did not increase the level of gut inflammation including COX-2 expression, AOM increased crypt......Severe combined immunodeficiency (SCID) mice transplanted with CD4+ T cells depleted of CD25+ regulatory T cells develop colitis within 2-3 weeks after the T cell transfer. In the present study we studied the effect of the carcinogen azoxymethane (AOM) on the colon crypt pathology of normal SCID...... changes associated with colon inflammation such as a decline in crypt numbers and an increase in crypts width throughout the large intestine. Thus it appears that AOM lower the threshold level for inflammation-induced changes which potentially may lead to neoplasia....

  2. Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism.

    Science.gov (United States)

    Redwan, Elrashdy M; Linjawi, Moustafa H; Uversky, Vladimir N

    2016-03-17

    Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species with high binding affinity to the insulin-like growth factor 1 (IGF1) receptor. The question we are trying to answer in this work is: are there any specific features of the distribution of intrinsic disorder propensity within the amino acid sequences of insulin analogues that may provide an explanation for the carcinogenicity of the altered insulin protein?

  3. The carcinogenicity of the biocide ortho-phenylphenol.

    Science.gov (United States)

    Appel, K E

    2000-04-01

    The biocides ortho-phenylphenol and its sodium salt (OPP and SOPP) are widely used as fungicides and antibacterial agents for commercial and consumer purposes. The carcinogenicity of OPP/SOPP toward the urinary bladder was demonstrated when rats were chronically fed concentrations of 0.5%-4% in their diet. Other species tested so far did not develop tumours. Understanding the mechanisms underlying OPP/SOPP-induced bladder carcinogenesis is critical to determine whether risks observed at high doses in rats are of relevance to humans exposed at much lower levels. This overview details experimental studies of carcinogenicity, genotoxicity as well as metabolism/toxicokinetics and other mechanistic studies which bear on cancer hazard and risk evaluation of exposure to humans. Based on the presently available knowledge, it is concluded that reactive quinoid metabolites exhibiting redox cycling activities are the crucial factors. At certain concentration levels, these metabolites are able to produce cytotoxic events with concomitant enhanced cell proliferation of the target tissue. Further important risk factors are probably promutagenic lesions induced by oxidative stress and a higher urinary pH. Supposed that these mechanisms are the basis for the tumourigenicity observed, then suitable low doses of OPP/SOPP will practically pose no cancer risk.

  4. Rodent-borne diseases and their risks for public health

    NARCIS (Netherlands)

    Meerburg, B.G.; Singleton, G.R.; Kijlstra, A.

    2009-01-01

    Rodents are the most abundant and diversified order of living mammals in the world. Already since the Middle Ages we know that they can contribute to human disease, as black rats were associated with distribution of plague. However, also in modern times rodents form a threat for public health. In

  5. Towards sustainable management of rodents in organic animal husbandry

    NARCIS (Netherlands)

    Meerburg, B.G.; Bonde, M.; Brom, F.W.A.; Endepols, S.; Jensen, A.N.; Leirs, H.; Lodal, J.; Singleton, G.R.; Pelz, H.J.; Rodenburg, T.B.; Kijlstra, A.

    2004-01-01

    From 26 to 28 May 2004 an international seminar was held in Wageningen, the Netherlands, about current knowledge and advice on rodent management on organic pig and poultry farms in Western Europe. This paper summarizes the discussions. Rodent management is necessary to protect the food production ch

  6. Rodent-borne diseases and their risks for public health

    NARCIS (Netherlands)

    Meerburg, B.G.; Singleton, G.R.; Kijlstra, A.

    2009-01-01

    Rodents are the most abundant and diversified order of living mammals in the world. Already since the Middle Ages we know that they can contribute to human disease, as black rats were associated with distribution of plague. However, also in modern times rodents form a threat for public health. In th

  7. Measuring behaviour in rodents: towards translational neuropsychiatric research

    NARCIS (Netherlands)

    Homberg, J.R.

    2013-01-01

    Rodent behavioural tasks are indispensable to advance the understanding of gene x environment interactions in neuropsychiatric disorders and the discovery of new therapeutic strategies. Yet, the actual translation of rodent data to humans, and thereby the understanding of the pathophysiology of neur

  8. Public Health and Rodents: A Game of Cat and Mouse

    NARCIS (Netherlands)

    Meerburg, B.G.

    2015-01-01

    Rodents are the most abundant order of living mammals, distributed on every continent except Antarctic and represent 43 % of all mammalian species. Beside causing food losses and infrastructural damage, rodents can harbour pathogens that may cause serious problems to human and animal health. Unfortu

  9. Evaluating effects of EPO in rodent behavioral assays related to depression.

    Science.gov (United States)

    Duman, Catharine H; Newton, Samuel S

    2013-01-01

    The cytokine erythropoietin (EPO) is an important regulator of hematopoesis and has well-known tissue protective properties. Neurotrophic action is implicated as mechanistically important in the treatment of depression, and neurotrophic actions of EPO suggest potential therapeutic utility of an EPO-like mechanism in depressive disorder. Rodent behavioral models that are responsive to clinically used antidepressants as well as to neurotrophic compounds can be used to assess potential antidepressant properties of EPO and EPO-like compounds. Rodent models described here are the forced-swim test (FST), a hyponeophagia test and the novel object recognition test. Each of these models provides different information and relevance to depression and each can be tested with EPO and similar compounds.

  10. Human exposure to carcinogenic heterocyclic amines and their mutational fingerprints in experimental animals.

    Science.gov (United States)

    Nagao, M; Wakabayashi, K; Ushijima, T; Toyota, M; Totsuka, Y; Sugimura, T

    1996-01-01

    Heterocyclic amines (HCAs) are mutagens/carcinogens to which humans are exposed on almost a daily basis. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) is the most abundant of the various carcinogenic HCAs (present at a level of 0.56 to 69.2 ng/g of cooked meat or fish), with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) following it at 0.64 to 6.44 ng/g. HCAs have been found in the urine of healthy people who consume ordinary diets, while patients receiving parenteral alimentation lack, for example, PhlP and MelQx in their urine. Based on the concentrations of PhlP and MelQx in urine samples from 10 healthy volunteers, daily intake of MelQx in Japanese was calculated to be 0.3 to 3.9 micrograms/person, while that of PhlP was 0.005 to 0 micrograms. The Japanese consume more MelQx than Americans, whereas Japanese intake of PhlP was about one-third that of Americans. MelQx-DNA adducts have also detected in Japanese Kidney, colon, and rectum samples using the 32P-postlabeling method followed by identification using high-performance liquid chromatography (HPLC) analysis; the levels were 0.18, 1.8, and 1.4 per 10(9) nucleotides, respectively. In addition, we elucidated the mutational fingerprints of Phlp by analyzing Apc mutations in rat colon cancers induced by this carcinogen. Four of eight tumors had a total of five mutations in the Apc gene, four of which featured a guanine deletion from 5'-GTGGGAT-3' sequences. This specific mutation spectrum may be used as a fingerprint of PhlP in evaluating its risk potential for human colon carcinogenesis. Mutations were not found in similar 2-amino-3-methylimidazo[4,5-f]quinoline-induced colon lesions. Microsatellite instability was detected in both colon and mammary tumors induced by PhlP. The mechanisms involved in this development of microsatellite instability in PhlP. The mechanisms involved in this development of microsatellite instability in PhlP-induced cancers remain to be elucidated. Images Figure 1

  11. Detection of Bartonella spp. in wild rodents in Israel using HRM real-time PCR.

    Science.gov (United States)

    Morick, Danny; Baneth, Gad; Avidor, Boaz; Kosoy, Michael Y; Mumcuoglu, Kosta Y; Mintz, Dvir; Eyal, Osnat; Goethe, Ralph; Mietze, Andreas; Shpigel, Nahum; Harrus, Shimon

    2009-11-18

    The prevalence of Bartonella spp. in wild rodents was studied in 19 geographical locations in Israel. One hundred and twelve rodents belonging to five species (Mus musculus, Rattus rattus, Microtus socialis, Acomys cahirinus and Apodemus sylvaticus) were included in the survey. In addition, 156 ectoparasites were collected from the rodents. Spleen sample from each rodent and the ectoparasites were examined for the presence of Bartonella DNA using high resolution melt (HRM) real-time PCR. The method was designed for the simultaneous detection and differentiation of eight Bartonella spp. according to the nucleotide variation in each of two gene fragments (rpoB and gltA) and the 16S-23S intergenic spacer (ITS) locus, using the same PCR protocol which allowed the simultaneous amplification of the three different loci. Bartonella DNA was detected in spleen samples of 19 out of 79 (24%) black rats (R. rattus) and in 1 of 4 (25%) Cairo spiny mice (A. cahirinus). In addition, 15 of 34 (44%) flea pools harbored Bartonella DNA. Only rat flea (Xenopsyla cheopis) pools collected from black rats (R. rattus) were positive for Bartonella DNA. The Bartonella sp. detected in spleen samples from black rats (R. rattus) was closely related to both B. tribocorum and B. elizabethae. The species detected in the Cairo spiny mouse (A. cahirinus) spleen sample was closely related to the zoonotic pathogen, B. elizabethae. These results indicate that Bartonella species are highly prevalent in suburban rodent populations and their ectoparasites in Israel. Further investigation of the prevalence and zoonotic potential of the Bartonella species detected in the black rats and the Cairo spiny mouse is warranted.

  12. Incorporating insect infestation into rodent seed dispersal: better if the larva is still inside.

    Science.gov (United States)

    Perea, Ramón; López, David; San Miguel, Alfonso; Gil, Luis

    2012-11-01

    Many nutritious seeds are commonly attacked by insects which feed on the seed reserves. However, studies have not fully explored the ecological implications of insect infestation in animal seed dispersal and subsequent plant regeneration. Our question is whether the fact that an infested seed still contains the larva or not might increase/decrease the probability of being successfully dispersed by animals. This study examines the effects of weevil-infested seeds on the natural regeneration of a rodent-dispersed oak species. Rodents showed a high ability to discriminate between sound and infested seeds, even when the larva was still inside. As a result, rodents caused differential seed dispersal for sound and infested seeds by modifying multiple aspects of the dispersal process. We found that, for the same seed weight, infested acorns with a larva still inside can contribute to natural regeneration (0.7 % of seedlings in next summer), although in comparison to sound acorns they suffered higher predation rates by rodents (both partial and complete), were removed later from the ground (less preferred), cached less frequently, and dispersed to shorter distances, which reduced their potential to colonize new environments. However, infested seeds with exit holes are notably less preferred by rodents and, when dispersed, they are mostly deposited on the litter (uncached) with shorter dispersal distances and lower emergence success. Thus, the probability that larval-holed acorns will produce viable seedlings is extremely low (null in this study). Whether infested seeds still contain a larva or not clearly determines the probability of being successfully dispersed. Premature seed drop prolongs the presence of the larva inside the acorn after seed drop, and could be a possible mechanism to allow dispersal of infested seeds.

  13. Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors.

    Science.gov (United States)

    Habert, René; Muczynski, Vincent; Grisin, Tiphany; Moison, Delphine; Messiaen, Sébastien; Frydman, René; Benachi, Alexandra; Delbes, Géraldine; Lambrot, Romain; Lehraiki, Abdelali; N'tumba-Byn, Thierry; Guerquin, Marie-Justine; Levacher, Christine; Rouiller-Fabre, Virginie; Livera, Gabriel

    2014-01-01

    Fetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk.

  14. Intraoperative cerebral blood flow imaging of rodents

    Science.gov (United States)

    Li, Hangdao; Li, Yao; Yuan, Lu; Wu, Caihong; Lu, Hongyang; Tong, Shanbao

    2014-09-01

    Intraoperative monitoring of cerebral blood flow (CBF) is of interest to neuroscience researchers, which offers the assessment of hemodynamic responses throughout the process of neurosurgery and provides an early biomarker for surgical guidance. However, intraoperative CBF imaging has been challenging due to animal's motion and position change during the surgery. In this paper, we presented a design of an operation bench integrated with laser speckle contrast imager which enables monitoring of the CBF intraoperatively. With a specially designed stereotaxic frame and imager, we were able to monitor the CBF changes in both hemispheres during the rodent surgery. The rotatable design of the operation plate and implementation of online image registration allow the technician to move the animal without disturbing the CBF imaging during surgery. The performance of the system was tested by middle cerebral artery occlusion model of rats.

  15. N-acetylcysteine (NAC) decreases binge eating in a rodent model

    OpenAIRE

    Hurley, Matthew M.; Resch, Jon M.; Maunze, Brian; Frenkel, Mogen M.; Baker, David A.; Choi, SuJean

    2016-01-01

    Binge eating behavior involves rapid consumption of highly palatable foods leading to increased weight gain. Feeding in binge disorders resembles other compulsive behaviors, many of which are responsive to N-acetyl cysteine (NAC), which is a cysteine prodrug often used to promote non-vesicular glutamate release by a cystine-glutamate antiporter. To examine the potential for NAC to alter a form of compulsive eating, we examined the impact of NAC on binge eating in a rodent model. Specifically,...

  16. Topographical organization of TRPV1-immunoreactive epithelium and CGRP-immunoreactive nerve terminals in rodent tongue

    OpenAIRE

    Kawashima, M.; Imura, K; Sato, I.

    2012-01-01

    Transient receptor potential vanilloid subfamily member 1 (TRPV1) is activated by capsaicin, acid, and heat and mediates pain through peripheral nerves. In the tongue, TRPV1 expression has been reported also in the epithelium. This indicates a possibility that sensation is first received by the epithelium. However, how nerves receive sensations from the epithelium remains unclear. To clarify the anatomical basis of this interaction, we performed immunohistochemical studies in the rodent tongu...

  17. Ecology of plague in Africa: response of indigenous wild rodents to experimental plague infection

    OpenAIRE

    Isaäcson, Margaretha; Taylor, Paul; Arntzen, Lorraine

    1983-01-01

    The Mastomys natalensis species complex, subdivided into genetically distinct species having diploid chromosome numbers 2n = 32 and 2n = 36, is a reservoir for several zoonoses including Lassa fever and plague. This report describes a study to determine whether these sibling species and three other rodent species have different potential as reservoirs for plague. It was found that M. natalensis (2n = 32) was significantly more resistant to experimental plague infection (50% survived inoculati...

  18. Interaction of Ionizing Radiation, Genetically Active Chemicals, and Radiofrequency Radiation in Human and Rodent Cells

    Science.gov (United States)

    1990-12-01

    Martin L. Meltz, Ph.D. Patricia K. Holahan , Ph.D. Steven T. Smith, Ph.D. James J. Kerbacher, Ph.D. Victor Ciaravino, Ph.D. Department of Radiology PO...Chemicals, and Radiofrequency Radiation in Human and Rodent Cells 12 PERSONAL AUTHOR(S) Meltz. Martin L.; Holahan Patricia K.; Smith Steven Kerbacher...Potentiation of SCE Induction and Cell Killing by Adriamycin in CHO Cells (Ciaravino and Holahan , in preparation), showed that Adriamycin exposure at 410C

  19. Rodent Models of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Philips, Thomas; Rothstein, Jeffrey D

    2015-06-01

    Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease affecting upper and lower motor neurons in the central nervous system. Patients with ALS develop extensive muscle wasting and atrophy leading to paralysis and death 3 to 5 years after disease onset. The condition may be familial (fALS 10%) or sporadic ALS (sALS, 90%). The large majority of fALS cases are due to genetic mutations in the Superoxide dismutase 1 gene (SOD1, 15% of fALS) and repeat nucleotide expansions in the gene encoding C9ORF72 (∼ 40% to 50% of fALS and ∼ 10% of sALS). Studies suggest that ALS is mediated through aberrant protein homeostasis (i.e., ER stress and autophagy) and/or changes in RNA processing (as in all non-SOD1-mediated ALS). In all of these cases, animal models suggest that the disorder is mediated non-cell autonomously, i.e., not only motor neurons are involved, but glial cells including microglia, astrocytes, and oligodendrocytes, and other neuronal subpopulations are also implicated in the pathogenesis. Provided in this unit is a review of ALS rodent models, including discussion of their relative advantages and disadvantages. Emphasis is placed on correlating the model phenotype with the human condition and the utility of the model for defining the disease process. Information is also presented on RNA processing studies in ALS research, with particular emphasis on the newest ALS rodent models. Copyright © 2013 John Wiley & Sons, Inc. All rights reserved.

  20. Carcinogenic risks associated with radiation pollution. [UV radiation, sunlight

    Energy Technology Data Exchange (ETDEWEB)

    Latarjet, R.

    1976-01-01

    The cancerogenic pollution by non-ionizing radiations is limited to the case of solar ultraviolet, whose activity at ground level may be increased as a consequence of the stratospheric depletion of ozone, produced by certain chemical pollutants: nitrogen oxides from supersonic aircrafts, freon. As regards ionizing radiations, the discussion is focused on the fundamental problem of the threshold, and on the means by which one may obtain some quantitative data related to carcinogenesis by small radiation doses in man. A new concept, that of a practical threshold, is proposed. A theory which links radiocancerogenesis, as well as chemical cancerogenesis, to errors produced in the repair of lesions in the DNA is discussed. The rads-equivalent project for chemical mutagens and carcinogens is described.

  1. [Thoughts on carcinogenic pollution caused by ionizing radiation].

    Science.gov (United States)

    Latarjet, R

    1976-01-01

    The pollution phenomenon groups the effects of small doses of radiation on large populations. These effects on Man are not directly accessible. One must: a) consider some epidemiological statistics (cosmic radiation at high altitudes; radioactivity from granitic surroundings); b) extrapolate from datas obtained with high doses; c) extrapolate from datas obtained with low doses in micro-organisms or mammalian cells in vitro. The interpolation scheme of Abrahamson et al. is so available for mutagenicity. The question of a threshold remains theoretical, although radiation-induced carcinogenesis often displays a dose-effects curve with a well market threshold. A new concept, that of a "practical threshold" is developped, which may be of great usefulness. The main genetic considerations are listed upon which the present international admissible doses are based. Finally, in order to establish quantitative comparisons between chemical and radiation carcinogenic pollution, the concept of "rad equivalents" for the main chemical mutagens is stressed.

  2. Carcinogenicity, allergenicity, and lupus-inducibility of arylamines.

    Science.gov (United States)

    Chung, King-Thom

    2016-01-01

    Arylamines are widely used in food, drugs, and cosmetics as well as other industries. These chemicals are present ubiquitously in cigarette smoke, smoke emitted from cooking fume hoods as well as are generated by diverse industries. Arylamines can be generated by cleavage of azo dyes by intestinal and skin microbiota. Some arylamines are used as drugs while others are constituents of human metabolism. Many of the arylamines are mutagenic and carcinogenic. They are generally recognized as the major cause of human bladder cancer, but arylamines can induce cancers of other organs in humans and animals. Some arylamines are allergenic, causing lupus like syndrome, or other maladies. In view of their unbiquitious nature and the diseases they cause, arylamines are probably the most important chemicals causing health problems.

  3. Retraction: Evaluation of carcinogenic effects of electromagnetic fields (EMF).

    Science.gov (United States)

    Mehic, Bakir

    2010-11-01

    The Editor-in-chief of the Bosnian Journal of Basic Medical Sciences has decided to retract the article from Bayazit V et al. [1] entitled as: "Evaluation of carcinogenic effects of electromagnetic fields (EMF)" published in Bosn J Basic Med Sci. 2010 Aug;10(3):245-50. After the editorial office was alerted of possible plagiarism in the article, it conducted thorough investigation and concluded that the article apparently represents plagiarized material from two World Health Organization reports, one European Commission report and other sources. Since this is considered scientific plagiarism and scientific misconduct, Editor-in-chief has decided to withdraw the article. The authors have agreed with the editorial office decision.

  4. Correspondence between flat aberrant crypt foci and mucin-depleted foci in rodent colon carcinogenesis.

    Science.gov (United States)

    Femia, Angelo Pietro; Paulsen, Jan Erik; Dolara, Piero; Alexander, Jan; Caderni, Giovanna

    2008-01-01

    Flat aberrant crypt foci (flat ACF) and mucin-depleted foci (MDF) are preneoplastic lesions identified in the colon of carcinogen-treated rodents stained with methylene blue (MB) and high iron diamine-alcian blue (HID-AB), respectively. The correspondence between flat ACF and MDF in the same colon of Min mice treated with azoxymethane (AOM) and of F344 rats treated with 1,2-dimethylhydrazine (DMH) was explored. The position of each flat ACF was recorded on a digitally constructed photographic map of the MB-stained colon. The same colons were then stained with HID-AB and the position of each MDF was compared with that of flat ACF. The fraction of coincident lesions, identified as both flat ACF and MDF with the two staining methods, was 57% and 42%, in the Min mice and F344 rats, respectively. Flat ACF or MDF not coincident with the two staining methods were either undetectable or ACF with one of the two methods. Flat ACF and MDF show considerable, but not total, overlap.

  5. [Evaluation of the carcinogenic effect of ceramic fibers in experiments on rats and mice].

    Science.gov (United States)

    Krajnow, A; Lao, I; Stetkiewicz, J

    1997-01-01

    The carcinogenic effect of Kaowoll raw and thermally used ceramic fibres was assessed in experiments on rats and mice. The fibers were applied intraperitoneally in doses by 25 and 5 mg,